A. D. Berendsen and B. R. Olsen, Bone development. Bone, vol.80, pp.14-22, 2015.

D. M. Ornitz and P. J. Marie, FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease, Genes Dev, vol.16, issue.12, pp.1446-1465, 2002.

F. Long and D. M. Ornitz, Development of the endochondral skeleton, Cold Spring Harb Perspect Biol. 1 janv, vol.5, issue.1, p.8334, 2013.

Y. Usami, A. T. Gunawardena, M. Iwamoto, and M. Enomoto-iwamoto, Wnt signaling in cartilage development and diseases: lessons from animal studies, Lab Invest. févr, vol.96, issue.2, pp.186-96, 2016.

F. Mallein-gerin and M. Van-der-rest, La culture de chondrocytes : outil d'analyse de la différenciation et de l'organisation moléculaire du cartilage. médecine/sciences, vol.12, p.1087, 1996.

B. Johnstone, M. Cucchiarini, G. Dodge, D. Eglin, F. Guilak et al., Tissue engineering for articular cartilage repair -the state of the art, Eur Cell Mater. 2 mai, vol.25, pp.248-67, 2013.

G. Musumeci, C. Loreto, R. Imbesi, F. M. Trovato, D. Giunta et al., Advantages of exercise in rehabilitation, treatment and prevention of altered morphological features in knee osteoarthritis. A narrative review, Histol Histopathol. juin, vol.29, issue.6, pp.707-726, 2014.

V. C. Mow and X. E. Guo, Mechano-Electrochemical Properties Of Articular Cartilage: Their Inhomogeneities and Anisotropies, Annu Rev Biomed Eng. août, vol.4, issue.1, pp.175-209, 2002.

R. Brocklehurst, M. T. Bayliss, A. Maroudas, H. L. Coysh, M. A. Freeman et al., The composition of normal and osteoarthritic articular cartilage from human knee joints. With special reference to unicompartmental replacement and osteotomy of the knee, J Bone Joint Surg Am. janv, vol.66, issue.1, pp.95-106, 1984.

Y. Nakagawa, T. Muneta, K. Otabe, N. Ozeki, M. Mizuno et al., Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and, In Vivo. Serra R, éditeur. PLOS ONE. 11 févr, vol.11, issue.2, p.148777, 2016.

G. A. Ateshian, W. H. Warden, J. J. Kim, R. P. Grelsamer, and V. C. Mow, Biphasic material properties articular cartilage compressioon experiments, vol.8, 1997.

C. T. Brighton, Morphology and biochemistry of the growth plate, Rheum Dis Clin North Am. avr, vol.13, issue.1, pp.75-100, 1987.

J. P. Iannotti, Growth plate physiology and pathology, Orthop Clin North Am. janv, vol.21, issue.1, pp.1-17, 1990.

. Schoenwolf, . Bleyl, and F. Brauer, Embryologie Humaine de larsen, 2017.

G. M. Behringer, K. Vintersten, and A. Nagy, Manipulating the Mouse Embryo : A laboratory Manual

E. Kozhemyakina, A. B. Lassar, and E. Zelzer, A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation, Development. 1 mars, vol.142, issue.5, pp.817-848, 2015.

A. E. , Remodeling potential of long bones following angular osteotomies, J Pediatr Orthop. févr, vol.9, issue.1, pp.37-43, 1989.

A. Alberty, J. Peltonen, and V. Ritsilä, Effects of distraction and compression on proliferation of growth plate chondrocytes. A study in rabbits, Acta Orthop Scand. août, vol.64, issue.4, pp.449-55, 1993.

E. B. Hunziker, Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes, Microsc Res Tech. 15 août, vol.28, issue.6, pp.505-524, 1994.

F. Rauch, Bone growth in length and width: the Yin and Yang of bone stability, J Musculoskelet Neuronal Interact. sept, vol.5, issue.3, pp.194-201, 2005.

N. F. Kember and K. Walker, Control of Bone Growth in Rats, Nature. févr, vol.229, issue.5284, p.428, 1971.

G. J. Breur, B. A. Vanenkevort, C. E. Farnum, and N. J. Wilsman, Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates, J Orthop Res, vol.9, issue.3, pp.348-59, 1991.

V. Abad, J. A. Uyeda, H. T. Temple, D. Luca, F. Baron et al., Determinants of Spatial Polarity in the Growth Plate, Endocrinology. 1 févr, vol.140, issue.2, pp.958-62, 1999.

V. Abad, J. L. Meyers, M. Weise, R. I. Gafni, K. M. Barnes et al., The Role of the Resting Zone in Growth Plate Chondrogenesis, Endocrinology. 1 mai, vol.143, issue.5, pp.1851-1858, 2002.

W. Bi, J. M. Deng, Z. Zhang, R. R. Behringer, and B. De-crombrugghe, Sox9 is required for cartilage formation, Nat Genet. mai, vol.22, issue.1, pp.85-94, 1999.

M. Wegner, From head to toes: the multiple facets of Sox proteins, Nucleic Acids Res. 15 mars, vol.27, issue.6, pp.1409-1429, 1999.

J. W. Foster, M. A. Dominguez-steglich, S. Guioli, C. Kwok, P. A. Weller et al., Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRYrelated gene, Nature. 8 déc, vol.372, issue.6506, pp.525-555, 1994.

T. Wagner, J. Wirth, J. Meyer, B. Zabel, M. Held et al., Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9, Cell. 16 déc, vol.79, issue.6, pp.1111-1131, 1994.

/. Pth-, Related Peptide Receptor Causing Blomstrand Lethal Osteochondrodysplasia, J Clin Endocrinol Metab, vol.84, issue.10, pp.3713-3733, 1999.

E. Schipani, K. Kruse, and H. Juppner, A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia, Science. 7 avr, vol.268, issue.5207, pp.98-100, 1995.

E. Schipani, C. B. Langman, A. M. Parfitt, G. S. Jensen, S. Kikuchi et al., Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone-Related Peptide in Jansen's Metaphyseal Chondrodysplasia, N Engl J Med. 5 sept, vol.335, issue.10, pp.708-722, 1996.

J. Guo, U. Chung, H. Kondo, F. R. Bringhurst, and H. M. Kronenberg, The PTH/PTHrP Receptor Can Delay Chondrocyte Hypertrophy In Vivo without Activating Phospholipase C, Dev Cell. 1 août, vol.3, issue.2, pp.183-94, 2002.

W. Huang, U. I. Chung, H. M. Kronenberg, and B. De-crombrugghe, The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones, Proc Natl Acad Sci, vol.98, issue.1, pp.160-165, 2001.

D. Huangfu and K. V. Anderson, Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates, Development. 1 janv, vol.133, issue.1, pp.3-14, 2006.

P. W. Ingham and A. P. Mcmahon, Hedgehog signaling in animal development: paradigms and principles, Genes Dev. 12 janv, vol.15, issue.23, pp.3059-87, 2001.

A. P. Mcmahon, P. W. Ingham, and C. J. Tabin, Developmental roles and clinical significance of Hedgehog signaling, Current Topics in Developmental Biology, pp.1-114, 2003.

. Long, Direct requirement for Ihh signaling in chondrocyte proliferation, vol.10, 2001.

M. J. Hilton, X. Tu, and F. Long, Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage, Dev Biol. 1 août, vol.308, issue.1, pp.93-105, 2007.

T. Kobayashi, Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP, J Clin Invest, vol.115, issue.7, pp.1734-1776, 2005.

S. J. Karp, E. Schipani, B. St-jacques, J. Hunzelman, H. Kronenberg et al., Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways, Development. 1 févr, vol.127, issue.3, pp.543-551, 2000.

H. M. Kronenberg, PTHrP and Skeletal Development, Ann N Y Acad Sci. 1 avr, vol.1068, issue.1, pp.1-13, 2006.

M. J. Hilton, X. Tu, J. Cook, H. Hu, and F. Long, Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development, Development, vol.132, pp.4339-51, 2005.

L. Koziel, M. Wuelling, S. Schneider, and A. Vortkamp, Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation, Development. 1 déc, vol.132, issue.23, pp.5249-60, 2005.

M. Ruat, L. Hoch, H. Faure, and D. Rognan, Structure du récepteur Smoothened. médecine/sciences, vol.29, pp.855-60, 2013.

P. Krejci, J. Prochazkova, J. Smutny, K. Chlebova, P. Lin et al., FGFR3 signaling induces a reversible senescence phenotype in chondrocytes similar to oncogene-induced premature senescence, Bone. juill, vol.47, issue.1, pp.102-112, 2010.

A. Beenken and M. Mohammadi, The FGF family: biology, pathophysiology and therapy, Nat Rev Drug Discov. mars, vol.8, issue.3, pp.235-53, 2009.

N. Itoh, Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, metabolism, and disease, Cell Tissue Res, vol.342, issue.1, pp.1-11, 2010.

N. Itoh and D. M. Ornitz, Functional evolutionary history of the mouse Fgf gene family, Dev Dyn, vol.237, issue.1, pp.18-27, 2008.

N. Itoh and D. M. Ornitz, Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease, J Biochem (Tokyo). 1 févr, vol.149, issue.2, pp.121-151, 2011.

S. Oulion, S. Bertrand, and H. Escriva, Evolution of the FGF Gene Family, Int J Evol Biol, p.298147, 2012.

F. Burdan, J. Szumi?o, A. Korobowicz, R. Farooquee, S. Patel et al., Morphology and physiology of the epiphyseal growth plate, Folia Histochem Cytobiol, vol.47, issue.1, pp.5-16, 2009.

S. Gong, Isoforms of receptors of fibroblast growth factors, J Cell Physiol. déc, vol.229, issue.12, pp.1887-95, 2014.

C. Powers, Fibroblast growth factors, their receptors and signaling, Endocr Relat Cancer. 1 sept, vol.7, issue.3, pp.165-97, 2000.

L. Dailey, D. Ambrosetti, A. Mansukhani, and C. Basilico, Mechanisms underlying differential responses to FGF signaling, Cytokine Growth Factor Rev. avr, vol.16, issue.2, pp.233-280, 2005.

D. M. Ornitz and N. Itoh, The Fibroblast Growth Factor signaling pathway, Wiley Interdiscip Rev Dev Biol. mai, vol.4, issue.3, pp.215-66, 2015.

X. Du, Y. Xie, C. J. Xian, and L. Chen, Role of FGFs/FGFRs in skeletal development and bone regeneration, J Cell Physiol, vol.227, issue.12, pp.3731-3774, 2012.

P. Krejci, B. Masri, L. Salazar, C. Farrington-rock, H. Prats et al., Bisindolylmaleimide I Suppresses Fibroblast Growth Factor-mediated Activation of Erk MAP Kinase in Chondrocytes by Preventing Shp2 Association with the Frs2 and Gab1 Adaptor Proteins, J Biol Chem. 2 févr, vol.282, issue.5, pp.2929-2965, 2007.

J. F. Fallon, A. Lopez, M. A. Ros, M. P. Savage, B. B. Olwin et al., FGF-2: apical ectodermal ridge growth signal for chick limb development, Science. 1 avr, vol.264, issue.5155, pp.104-111, 1994.

Y. Fei and M. M. Hurley, Role of fibroblast growth factor 2 and wnt signaling in anabolic effects of parathyroid hormone on bone formation, J Cell Physiol, vol.227, issue.11, pp.3539-3584, 2012.

A. Montero, Y. Okada, M. Tomita, M. Ito, H. Tsurukami et al., Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation, J Clin Invest. 15 avr, vol.105, issue.8, pp.1085-93, 2000.

F. V. Mariani, C. P. Ahn, and G. R. Martin, Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning, Nature. mai, vol.453, issue.7193, pp.401-406, 2008.

A. M. Moon, A. M. Boulet, and M. R. Capecchi, Normal limb development in conditional mutants of Fgf4, Development. 1 mars, vol.127, issue.5, pp.989-96, 2000.

A. M. Moon and M. R. Capecchi, Fgf8 is required for outgrowth and patterning of the limbs, Nat Genet. déc, vol.26, issue.4, pp.455-464, 2000.

I. H. Hung, K. Yu, K. J. Lavine, and D. M. Ornitz, FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod, Dev Biol. 15 juill, vol.307, issue.2, pp.300-313, 2007.

G. R. Martin, The roles of FGFs in the early development of vertebrate limbs, Genes Dev. 6 janv, vol.12, issue.11, pp.1571-86, 1998.

H. Ohuchi, T. Nakagawa, A. Yamamoto, A. Araga, T. Ohata et al., The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor, Development. 1 juin, vol.124, issue.11, pp.2235-2279, 1997.

X. Xu, M. Weinstein, C. Li, M. Naski, R. I. Cohen et al., Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction, Development. 15 févr, vol.125, issue.4, pp.753-65, 1998.

Z. Liu, J. Xu, J. S. Colvin, and D. M. Ornitz, Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18, Genes Dev. 4 janv, vol.16, issue.7, pp.859-69, 2002.

N. Ohbayashi, M. Shibayama, Y. Kurotaki, M. Imanishi, T. Fujimori et al., FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis, Genes Dev. 4 janv, vol.16, issue.7, pp.870-879, 2002.

L. F. Bonewald and M. J. Wacker, FGF23 production by osteocytes, Pediatr Nephrol. 1 avr, vol.28, issue.4, pp.563-571, 2013.

A. Raimann, D. A. Ertl, M. Helmreich, S. Sagmeister, M. Egerbacher et al., Fibroblast Growth Factor 23 and Klotho Are Present in the Growth Plate, Connect Tissue Res. 1 avr, vol.54, issue.2, pp.108-125, 2013.

L. Chen, D. Li, C. Li, A. Engel, and C. Deng, A Ser250Trp substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis, Bone. 1 août, vol.33, issue.2, pp.169-78, 2003.

C. Deng, A. Wynshaw-boris, F. Zhou, A. Kuo, and P. Leder, Fibroblast Growth Factor Receptor 3 Is a Negative Regulator of Bone Growth, Cell. 22 mars, vol.84, issue.6, pp.911-932, 1996.

M. Harada, H. Murakami, A. Okawa, N. Okimoto, S. Hiraoka et al., FGF9 monomer/dimer equilibrium regulates extracellular matrix affinity and tissue diffusion, Nat Genet. mars, vol.41, issue.3, pp.289-98, 2009.

T. Larsson, R. Marsell, E. Schipani, C. Ohlsson, Ö. Ljunggren et al., Transgenic Mice Expressing Fibroblast Growth Factor 23 under the Control of the ?1(I) Collagen Promoter Exhibit Growth Retardation, Osteomalacia, and Disturbed Phosphate Homeostasis, Endocrinology. 1 juill, vol.145, issue.7, pp.3087-94, 2004.

J. Wang, X. Du, C. Li, L. Yin, B. Chen et al.,

Z. Yi-xue, Yi Chuan Xue Za Zhi Zhonghua Yixue Yichuanxue Zazhi Chin, J Med Genet. déc, vol.21, issue.6, pp.537-578, 2004.

L. Xiao, A. Esliger, and M. M. Hurley, Nuclear FGF2 Isoforms Inhibit Bone Marrow Stromal Cell Mineralization through FGF23/FGFR/MAPK In Vitro, J Bone Miner Res Off J Am Soc Bone Miner Res. janv, vol.28, issue.1, pp.35-45, 2013.

Y. X. Zhou, X. Xu, L. Chen, C. Li, S. G. Brodie et al., A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures, Hum Mol Genet. 12 août, vol.9, issue.13, pp.2001-2009, 2000.

X. He, F. Xie, and Z. Ren, Rapid detection of G1138A and G1138C mutations of the FGFR3 gene in patients with achondroplasia using high-resolution melting analysis, Genet Test Mol Biomark. avr, vol.16, issue.4, pp.297-301, 2012.

P. Krejci, The paradox of FGFR3 signaling in skeletal dysplasia: Why chondrocytes growth arrest while other cells over proliferate, Mutat Res Mutat Res. 1 janv, vol.759, pp.40-48, 2014.

L. Chen, R. Adar, X. Yang, E. O. Monsonego, C. Li et al., Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis, J Clin Invest. 1 déc, vol.104, issue.11, pp.1517-1542, 1999.

M. C. Naski, J. S. Colvin, J. D. Coffin, and D. M. Ornitz, Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 15 déc, vol.125, pp.4977-88, 1998.

O. Segev, I. Chumakov, Z. Nevo, D. Givol, L. Madar-shapiro et al., Restrained chondrocyte proliferation and maturation with abnormal growth plate vascularization and ossification in human FGFR-3(G380R) transgenic mice, Hum Mol Genet. 22 janv, vol.9, issue.2, pp.249-58, 2000.

Y. Wang, M. K. Spatz, K. Kannan, H. Hayk, A. Avivi et al., A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3, Proc Natl Acad Sci. 13 avr, vol.96, issue.8, pp.4455-60, 1999.

T. Iwata, L. Chen, C. Li, D. A. Ovchinnikov, R. R. Behringer et al., A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos, Hum Mol Genet. 1 juill, vol.9, issue.11, pp.1603-1616, 2000.

C. Li, A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors, Hum Mol Genet. 1 janv, vol.8, issue.1, pp.35-44, 1999.

S. Murakami, Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype, Genes Dev. 1 févr, vol.18, issue.3, pp.290-305, 2004.

A. E. Denker, S. B. Nicoll, and R. S. Tuan, Formation of cartilage-like spheroids by micromass cultures of murine C3H10T1/2 cells upon treatment with transforming growth factor-?1, Differentiation. 1 juill, vol.59, issue.1, pp.25-34, 1995.

W. M. Kulyk, B. J. Rodgers, K. Greer, and R. A. Kosher, Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-?, Dev Biol, vol.135, issue.2, pp.424-454, 1989.

C. M. Leonard, H. M. Fuld, D. A. Frenz, S. A. Downie, J. Massague et al., Role of transforming growth factor-? in chondrogenic pattern formation in the embryonic limb: Stimulation of mesenchymal condensation and fibronectin gene expression by exogenenous TGF-? and evidence for endogenous TGF-?-like activity, Dev Biol. 1 mai, vol.145, issue.1, pp.99-109, 1991.

R. T. Ballock, A. Heydemann, L. M. Wakefield, K. C. Flanders, A. B. Roberts et al., TGF-?1 Prevents Hypertrophy of Epiphyseal Chondrocytes: Regulation of Gene Expression for Cartilage Matrix Proteins and Metalloproteases, Dev Biol. 1 août, vol.158, issue.2, pp.414-443, 1993.

K. Böhme, K. H. Winterhalter, and P. Bruckner, Terminal Differentiation of Chondrocytes in Culture Is a Spontaneous Process and Is Arrested by Transforming Growth Factor-?2 and Basic Fibroblast Growth Factor in Synergy, Exp Cell Res. 1 janv, vol.216, issue.1, pp.191-199, 1995.

S. C. Dieudonné, C. M. Semeins, S. W. Goei, S. Vukicevic, K. J. Nulend et al., Opposite effects of osteogenic protein and transforming growth factor ? on chondrogenesis in cultured long bone rudiments, J Bone Miner Res, vol.9, issue.6, pp.771-80, 1994.

Y. Kato, M. Iwamoto, T. Koike, F. Suzuki, and Y. Takano, Terminal differentiation and calcification in rabbit chondrocyte cultures grown in centrifuge tubes: regulation by transforming growth factor beta and serum factors, Proc Natl Acad Sci. 1 déc, vol.85, issue.24, pp.9552-9558, 1988.

T. Tschan, K. Böhme, M. Conscience-egli, G. Zenke, K. H. Winterhalter et al., Autocrine or paracrine transforming growth factor-beta modulates the phenotype of chick embryo sternal chondrocytes in serum-free agarose culture, J Biol Chem. 3 mai, vol.268, issue.7, pp.5156-61, 1993.

R. Tuli, S. Tuli, S. Nandi, X. Huang, P. A. Manner et al., Transforming Growth Factor-?-mediated Chondrogenesis of Human Mesenchymal Progenitor Cells Involves N-cadherin and Mitogen-activated Protein Kinase and Wnt Signaling Crosstalk, J Biol Chem, vol.278, issue.42, pp.41227-41263, 2003.

M. A. Cleary, G. Osch, . Van, P. A. Brama, C. A. Hellingman et al., TGF? and Wnt crosstalk: embryonic to in vitro cartilage development from mesenchymal stem cells, J Tissue Eng Regen Med, vol.9, issue.4, pp.332-374, 2013.

R. Serra, M. Johnson, E. H. Filvaroff, J. Laborde, D. M. Sheehan et al., Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal

J. A. Buckwalter, Maintaining and restoring mobility in middle and old age: the importance of the soft tissues, Instr Course Lect, vol.46, pp.459-69, 1997.

J. A. Buckwalter and H. J. Mankin, Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation, Instr Course Lect, vol.47, pp.487-504, 1998.

A. M. Bhosale and J. B. Richardson, Articular cartilage: structure, injuries and review of management, Br Med Bull. 1 sept, vol.87, issue.1, pp.77-95, 2008.

P. Castagnola, B. Dozin, G. Moro, and R. Cancedda, Changes in the expression of collagen genes show two stages in chondrocyte differentiation in vitro, J Cell Biol. 1 févr, vol.106, issue.2, pp.461-468, 1988.

K. Iyama, Y. Ninomiya, B. R. Olsen, T. F. Linsenmayer, R. L. Trelstad et al., Spatiotemporal pattern of type X collagen gene expression and collagen deposition in embryonic chick vertebrae undergoing endochondral ossification, Anat Rec. 1 avr, vol.229, issue.4, pp.462-72, 1991.

Y. Li, D. A. Lacerda, M. L. Warman, D. R. Beier, H. Yoshioka et al., A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis, Cell. 10 févr, vol.80, issue.3, pp.423-453, 1995.

B. R. Olsen, New insights into the function of collagens from genetic analysis, Curr Opin Cell Biol. 1 janv, vol.7, issue.5, pp.720-727, 1995.

R. Mayne and . Cartilage, What Is Their Function, and Are They Involved in Articular Disease?, Arthritis Rheum, vol.32, issue.3, pp.241-247, 1989.

M. Godfrey and D. W. Hollister, Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen, Am J Hum Genet. déc, vol.43, issue.6, pp.904-917, 1988.

J. Körkkö, D. H. Cohn, L. Ala-kokko, D. Krakow, and D. J. Prockop, Widely distributed mutations in the COL2A1 gene produce achondrogenesis type II/hypochondrogenesis, Am J Med Genet, vol.92, issue.2, pp.95-100, 2000.

D. J. Wilkin, A. S. Artz, S. South, R. S. Lachman, D. L. Rimoin et al., Small deletions in the type II collagen triple helix produce Kniest dysplasia, Am J Med Genet, vol.85, issue.2, pp.105-117, 1999.

D. J. Wilkin, R. Liberfarb, J. Davis, H. P. Levy, W. G. Cole et al., Rapid determination of COL2A1 mutations in individuals with Stickler syndrome: Analysis of potential premature termination codons, Am J Med Genet, vol.94, issue.2, pp.141-149, 2000.

G. E. Tiller, P. A. Polumbo, M. A. Weis, R. Bogaert, R. S. Lachman et al., Dominant mutations in the type II collagen gene, COL2A1 , produce spondyloepimetaphyseal dysplasia, Strudwick type, Nat Genet. sept, vol.11, issue.1, p.87, 1995.

K. Gelse, E. Pöschl, and T. Aigner, Collagens-structure, function, and biosynthesis. Adv Drug Deliv Rev, vol.55, pp.1531-1577, 2003.

Q. Zheng, E. Sebald, G. Zhou, Y. Chen, W. Wilcox et al., Dysregulation of Chondrogenesis in Human Cleidocranial Dysplasia, Am J Hum Genet. 1 août, vol.77, issue.2, pp.305-317, 2005.

J. Gu, Y. Lu, F. Li, L. Qiao, Q. Wang et al., Identification and characterization of the novel Col10a1 regulatory mechanism during chondrocyte hypertrophic differentiation, Cell Death Dis. oct, vol.5, issue.10, p.1469, 2014.

Q. Zheng, G. Zhou, R. Morello, Y. Chen, X. Garcia-rojas et al., Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo, J Cell Biol. 1 sept, vol.162, issue.5, pp.833-875, 2003.

F. Mwale, P. Girard-lauriault, H. T. Wang, S. Lerouge, J. Antoniou et al., Suppression of genes related to hypertrophy and osteogenesis in committed human mesenchymal stem cells cultured on novel nitrogen-rich plasma polymer coatings, Tissue Eng. sept, vol.12, issue.9, pp.2639-2686, 2006.

A. Petit, H. T. Wang, P. Girard-lauriault, M. R. Wertheimer, J. Antoniou et al., Novel insights into the mechanism of decreased expression of type X collagen in human mesenchymal stem cells from patients with osteoarthritis cultured on nitrogen-rich plasma polymers: Implication of cyclooxygenase-1, J Biomed Mater Res A, vol.94, issue.3, pp.744-50, 2010.

J. R. Couchman, Transmembrane Signaling Proteoglycans. Annu Rev Cell Dev Biol, vol.26, issue.1, pp.89-114, 2010.

R. V. Iozzo and L. Schaefer, Proteoglycan form and function: A comprehensive nomenclature of proteoglycans, Matrix Biol. mars, vol.42, pp.11-55, 2015.

K. Prydz and K. T. Dalen, Synthesis and sorting of proteoglycans, J Cell Sci. 15 janv, vol.113, issue.2, pp.193-205, 2000.

M. K. Cowman, H. Lee, K. L. Schwertfeger, J. B. Mccarthy, and E. A. Turley, The Content and Size of Hyaluronan in Biological Fluids and Tissues, Front Immunol, vol.6, 2015.

M. Bilandzic and K. L. Stenvers, Betaglycan: A multifunctional accessory, Mol Cell Endocrinol. 6 juin, vol.339, issue.1, pp.180-189, 2011.

A. Hildebrand, M. Romarís, L. M. Rasmussen, D. Heinegård, D. R. Twardzik et al., Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor ?, Biochem J. 1 sept, vol.302, issue.2, pp.527-561, 1994.

X. Lin, Functions of heparan sulfate proteoglycans in cell signaling during development, Development. 15 déc, vol.131, issue.24, pp.6009-6030, 2004.

D. M. Ornitz, FGFs, heparan sulfate and FGFRs: complex interactions essential for development, BioEssays. 31 janv, vol.22, issue.2, pp.108-120, 2000.

N. S. Gandhi and R. L. Mancera, The Structure of Glycosaminoglycans and their Interactions with Proteins, Chem Biol Drug Des. 1 déc, vol.72, issue.6, pp.455-82, 2008.

S. O. Kolset and G. Pejler, Serglycin: A Structural and Functional Chameleon with Wide Impact on Immune Cells, J Immunol, vol.15, issue.10, pp.4927-4960, 2011.

B. G. Gibson and M. D. Briggs, The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases, Orphanet J Rare Dis. 28 juin, vol.11, issue.1, p.86, 2016.

C. B. Knudson and W. Knudson, Cartilage proteoglycans. Semin Cell Dev Biol. 1 avr, vol.12, issue.2, pp.69-78, 2001.

V. Glumoff, M. Savontaus, J. Vehanen, and E. Vuorio, Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by Northern and in situ hybridization using species specific cDNA probes, Biochim Biophys Acta BBA -Gene Struct Expr, vol.22, issue.3, pp.613-635, 1994.

S. W. Tompson, B. Merriman, V. A. Funari, M. Fresquet, R. S. Lachman et al., A Recessive Skeletal Dysplasia, SEMD Aggrecan Type, Results from a Missense Mutation Affecting the C-Type Lectin Domain of Aggrecan, Am J Hum Genet. 9 janv, vol.84, issue.1, pp.72-81, 2009.

H. Watanabe, K. Kimata, S. Line, D. Strong, L. Gao et al., Mouse cartilage matrix deficiency ( cmd ) caused by a 7 bp deletion in the aggrecan gene, Nat Genet. juin, vol.7, issue.2, p.154, 1994.

H. Watanabe, K. Nakata, K. Kimata, I. Nakanishi, and Y. Yamada, Dwarfism and ageassociated spinal degeneration of heterozygote cmd mice defective in aggrecan, Proc Natl Acad Sci. 24 juin, vol.94, issue.13, pp.6943-6950, 1997.

J. M. Day, A. I. Olin, A. D. Murdoch, A. Canfield, T. Sasaki et al., Alternative Splicing in the Aggrecan G3 Domain Influences Binding Interactions with Tenascin-C and Other Extracellular Matrix Proteins, J Biol Chem. 26 mars, vol.279, issue.13, pp.12511-12519, 2004.

H. M. Kronenberg, Developmental regulation of the growth plate, Nature. mai, vol.423, issue.6937, pp.332-338, 2003.

Y. Maeda, E. Nakamura, M. Nguyen, L. J. Suva, F. L. Swain et al., Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone, Proc Natl Acad Sci. 10 avr, vol.104, issue.15, pp.6382-6389, 2007.

M. S. Domowicz, M. Cortes, J. G. Henry, and N. B. Schwartz, Aggrecan modulation of growth plate morphogenesis, Dev Biol. 15 mai, vol.329, issue.2, pp.242-57, 2009.

D. Yan and X. Lin, Shaping Morphogen Gradients by Proteoglycans, Cold Spring Harb Perspect Biol. 9 janv, vol.1, issue.3, p.2493, 2009.

P. Kischel, D. Waltregny, B. Dumont, A. Turtoi, Y. Greffe et al., Versican overexpression in human breast cancer lesions: Known and new isoforms for stromal tumor targeting, Int J Cancer, vol.126, issue.3, pp.640-50, 2010.

T. N. Wight, I. Kang, and M. J. Merrilees, Versican and the control of inflammation, Matrix Biol. 1 avr, vol.35, pp.152-61, 2014.

K. Kimata, Y. Oike, K. Tani, T. Shinomura, M. Yamagata et al., A large chondroitin sulfate proteoglycan (PG-M) synthesized before chondrogenesis in the limb bud of chick embryo, J Biol Chem, vol.261, issue.29, pp.13517-13542, 1986.

T. Shinomura, Y. Nishida, K. Ito, and K. Kimata, cDNA cloning of PG-M, a large chondroitin sulfate proteoglycan expressed during chondrogenesis in chick limb buds. Alternative spliced multiforms of PG-M and their relationships to versican, J Biol Chem. 7 mai, vol.268, pp.14461-14470, 1993.

N. B. Schwartz, A. K. Hennig, R. C. Krueger, M. Krzystolik, H. Li et al., Developmental expression of S103L cross-reacting proteoglycans in embryonic chick, Prog Clin Biol Res, vol.383, pp.505-519, 1993.

A. D. Theocharis, S. S. Skandalis, G. N. Tzanakakis, and N. K. Karamanos, Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting, FEBS J, vol.277, pp.3904-3927, 2010.

Y. Choi, H. Chung, H. Jung, J. R. Couchman, and E. Oh, Syndecans as cell surface receptors: Unique structure equates with functional diversity, Matrix Biol. 1 mars, vol.30, issue.2, pp.93-102, 2011.

T. Pap and J. Bertrand, Syndecans in cartilage breakdown and synovial inflammation, Nat Rev Rheumatol. janv, vol.9, issue.1, pp.43-55, 2013.

T. Manon-jensen, Y. Itoh, and J. R. Couchman, Proteoglycans in health and disease: the multiple roles of syndecan shedding, FEBS J, vol.277, pp.3876-89, 2010.

A. Fico, F. Maina, and R. Dono, Fine-tuning of cell signaling by glypicans, Cell Mol Life Sci CMLS. mars, vol.68, issue.6, pp.923-932, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00202709

J. Filmus, M. Capurro, and R. J. Glypicans, Genome Biol. 22 mai, vol.9, issue.5, p.224, 2008.

K. Mythreye and G. C. Blobe, The type III TGF-? receptor regulates epithelial and cancer cell migration through ?-arrestin2-mediated activation of Cdc42, Proc Natl Acad Sci, vol.106, issue.3, pp.8221-8227, 2009.

P. J. Roughley, The structure and function of cartilage proteoglycans. Eur Cell Mater, vol.12, pp.92-101, 2006.

J. E. Scott, Proteodermatan and Proteokeratan Sulfate (Decorin, Lumican/Fibromodulin) Proteins Are Horseshoe Shaped. Implications for Their Interactions with Collagen, Biochemistry. 1 janv, vol.35, issue.27, pp.8795-8804, 1996.

J. D. Gregory, T. C. Laurent, and L. Rodén, Enzymatic Degradation of Chondromucoprotein, J Biol Chem. 10 janv, vol.239, issue.10, pp.3312-3332, 1964.

E. E. Grebner, C. W. Hall, and E. F. Neufeld, Glycosylation of serine residues by a uridine diphosphate-xylose: Protein xylosyltransferase from mouse mastocytoma, Arch Biochem Biophys. 1 janv, vol.116, pp.391-399, 1966.

E. E. Grebner, C. W. Hall, and E. F. Neufeld, Incorporation of D-xylose-C14 into glycoprotein by particles from hen oviduct, Biochem Biophys Res Commun. 22 mars, vol.22, issue.6, pp.672-679, 1966.

J. R. Baker, L. Rodén, and A. C. Stoolmiller, Biosynthesis of Chondroitin Sulfate Proteoglycan xylosyl transfer to smith-dgraded cartilage proteoglycan and other exogenous acceptors, J Biol Chem. 25 juin, vol.247, issue.12, pp.3838-3885, 1972.

S. C. Campbell, R. C. Krueger, and N. B. Schwartz, Deglycosylation of chondroitin sulfate proteoglycan and derived peptides, Biochemistry. 30 janv, vol.29, issue.4, pp.907-921, 1990.

T. Brinkmann, C. Weilke, and K. Kleesiek, Recognition of Acceptor Proteins by UDP-Dxylose Proteoglycan Core Protein ?-D-Xylosyltransferase, J Biol Chem. 25 avr, vol.272, issue.17, pp.11171-11176, 1997.

P. Campbell, I. Jacobsson, L. Benzing-purdie, L. Rodén, and J. H. Fessler, Silk-A new substrate for UDP-d-xylose: Proteoglycan core protein ?-d-xylosyltransferase, Anal Biochem. 1 mars, vol.137, issue.2, pp.505-521, 1984.

D. M. Mann, Y. Yamaguchi, M. A. Bourdon, and E. Ruoslahti, Analysis of glycosaminoglycan substitution in decorin by site-directed mutagenesis, J Biol Chem. 25 mars, vol.265, issue.9, pp.5317-5340, 1990.

I. Wilson, The never-ending story of peptide O-xylosyltransferase, Cell Mol Life Sci CMLS. avr, vol.61, issue.7-8, pp.794-809, 2004.

S. Huber, K. H. Winterhalter, and L. Vaughan, Isolation and sequence analysis of the glycosaminoglycan attachment site of type IX collagen, J Biol Chem. 15 janv, vol.263, issue.2, pp.752-758, 1988.

C. Götting, J. Kuhn, R. Zahn, T. Brinkmann, and K. Kleesiek, Molecular Cloning and Expression of Human UDP-d-Xylose:Proteoglycan Core Protein ?-dXylosyltransferase and its First Isoform XT-II, J Mol Biol. déc, vol.304, issue.4, pp.517-545, 2000.

K. Cuellar, H. Chuong, S. M. Hubbell, and M. E. Hinsdale, Biosynthesis of Chondroitin and Heparan Sulfate in Chinese Hamster Ovary Cells Depends on Xylosyltransferase II, J Biol Chem. 23 févr, vol.282, issue.8, pp.5195-200, 2007.

C. Pönighaus, A. M. Casanova, J. C. Prante, C. Kuhn, J. Esko et al., Human xylosyltransferase II is involved in the biosynthesis of the uniform tetrasaccharide linkage region in chondroitin sulfate and heparan sulfate proteoglycans, J Biol Chem. 23 févr, vol.282, issue.8, pp.5201-5207, 2007.

J. Voglmeir, R. Voglauer, and I. Wilson, XT-II, the second isoform of human peptide-Oxylosyltransferase, displays enzymatic activity, J Biol Chem. 2 mars, vol.282, issue.9, pp.5984-90, 2007.

C. Roch, J. Kuhn, K. Kleesiek, and C. Götting, Differences in gene expression of human xylosyltransferases and determination of acceptor specificities for various proteoglycans, Biochem Biophys Res Commun. 1 janv, vol.391, issue.1, pp.685-91, 2010.

C. Breton, E. Bettler, D. H. Joziasse, R. A. Geremia, and A. Imberty, Sequence-Function Relationships of Prokaryotic and Eukaryotic Galactosyltransferases, J Biochem (Tokyo), vol.123, issue.6, pp.1000-1009, 1998.
URL : https://hal.archives-ouvertes.fr/hal-00314475

C. Wiggins and S. Munro, Activity of the yeast MNN1 ?-1,3-mannosyltransferase requires a motif conserved in many other families of glycosyltransferases, Proc Natl Acad Sci. 7 juill, vol.95, issue.14, pp.7945-50, 1998.

C. Götting, S. Müller, M. Schöttler, S. Schön, C. Prante et al., Analysis of the DXD motifs in human xylosyltransferase I required for enzyme activity, J Biol Chem, vol.279, issue.41, pp.42566-73, 2004.

S. Müller, J. Disse, M. Schöttler, S. Schön, C. Prante et al., Human xylosyltransferase I and N-terminal truncated forms: functional characterization of the core enzyme, Biochem J. 15 févr, vol.394, pp.163-71, 2006.

E. H. Holmes, T. Y. Yen, S. Thomas, R. Joshi, A. Nguyen et al., Human alpha 1,3/4 fucosyltransferases. Characterization of highly conserved cysteine residues and Nlinked glycosylation sites, J Biol Chem. 11 août, vol.275, issue.32, pp.24237-24282, 2000.
URL : https://hal.archives-ouvertes.fr/hal-01211856

Y. Wang, S. S. Wong, M. N. Fukuda, H. Y. Zu, Z. D. Liu et al., Identification of Functional Cysteine Residues in Human Galactosyltransferase, Biochem Biophys Res Commun, vol.204, issue.2, pp.701-710, 1994.

S. Müller, M. Schöttler, S. Schön, C. Prante, T. Brinkmann et al., Human xylosyltransferase I: functional and biochemical characterization of cysteine residues required for enzymic activity, Biochem J. 1 mars, vol.386, pp.227-263, 2005.

D. C. Briggs and E. Hohenester, Structural Basis for the Initiation of Glycosaminoglycan Biosynthesis by Human Xylosyltransferase 1. Struct Lond Engl 1993. 5 juin, vol.26, pp.801-809, 2018.

M. Aebi, N-linked protein glycosylation in the ER, Biochim Biophys Acta BBA -Mol Cell Res, vol.1833, issue.11, pp.2430-2437, 2013.

N. Nuwayhid, J. H. Glaser, J. C. Johnson, H. E. Conrad, S. C. Hauser et al., Xylosylation and glucuronosylation reactions in rat liver Golgi apparatus and endoplasmic reticulum, J Biol Chem. 10 mai, vol.261, issue.28, pp.12936-12977, 1986.

L. S. Lohmander, T. Shinomura, V. C. Hascall, and J. H. Kimura, Xylosyl transfer to the core protein precursor of the rat chondrosarcoma proteoglycan, J Biol Chem. 11 mai, vol.264, issue.31, pp.18775-80, 1989.

A. L. Horwitz and A. Dorfman, Subcelluar Sites for Synthesis of Chondromucoprotein of Cartilage, J Cell Biol. 1 août, vol.38, issue.2, pp.358-68, 1968.

H. P. Hoffmann, N. B. Schwartz, L. Rodén, and D. J. Prockop, Location of xylosyltransferase in the cisternae of the rough endoplasmic reticulum of embryonic cartilage cells, Connect Tissue Res, vol.12, issue.2, pp.151-63, 1984.

B. M. Vertel, L. M. Walters, N. Flay, A. E. Kearns, and N. B. Schwartz, Xylosylation is an endoplasmic reticulum to Golgi event, J Biol Chem. 25 mai, vol.268, issue.15, pp.11105-11117, 1993.

A. E. Kearns, B. M. Vertel, and N. B. Schwartz, Topography of glycosylation and UDP-xylose production, J Biol Chem. 25 mai, vol.268, issue.15, pp.11097-104, 1993.

S. Schön, C. Prante, C. Bahr, J. Kuhn, K. Kleesiek et al., Cloning and recombinant expression of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II, J Biol Chem. 19 mai, vol.281, issue.20, pp.14224-14255, 2006.

E. Condac, R. Silasi-mansat, S. Kosanke, T. Schoeb, R. Towner et al., Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating enzyme of glycosaminoglycan biosynthesis, Proc Natl Acad Sci. 29 mai, vol.104, issue.22, pp.9416-9437, 2007.

C. Götting, J. Kuhn, and K. Kleesiek, Human xylosyltransferases in health and disease, Cell Mol Life Sci. juin, vol.64, issue.12, pp.1498-517, 2007.

E. Condac, G. L. Dale, D. Bender-neal, B. Ferencz, R. Towner et al.,

, Xylosyltransferase II is a significant contributor of circulating xylosyltransferase levels and platelets constitute an important source of xylosyltransferase in serum, Glycobiology. août, vol.19, issue.8, pp.829-862, 2009.

J. Kuhn, C. Götting, B. J. Beahm, C. R. Bertozzi, I. Faust et al., Xylosyltransferase II is the predominant isoenzyme which is responsible for the steady-state level of xylosyltransferase activity in human serum, Biochem Biophys Res Commun. 10 avr, vol.459, issue.3, pp.469-74, 2015.

C. F. Munns, S. Fahiminiya, N. Poudel, M. C. Munteanu, J. Majewski et al., Homozygosity for Frameshift Mutations in XYLT2 Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects, Am J Hum Genet. 4 juin, vol.96, issue.6, pp.971-979, 2015.

J. Schreml, B. Durmaz, O. Cogulu, K. Keupp, F. Beleggia et al., The missing "link": an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation, Hum Genet, vol.133, issue.1, pp.29-39, 2013.

C. Bui, C. Huber, B. Tuysuz, Y. Alanay, C. Bole-feysot et al., XYLT1 Mutations in Desbuquois Dysplasia Type 2, Am J Hum Genet. 6 mars, vol.94, issue.3, pp.405-419, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01704452

S. Van-koningsbruggen, H. Knoester, R. Bakx, O. Mook, L. Knegt et al., Complete and partial XYLT1 deletion in a patient with neonatal short limb skeletal dysplasia, Am J Med Genet A, vol.170, issue.2, pp.510-514, 2015.

L. Guo, N. H. Elcioglu, A. Iida, Y. K. Demirkol, S. Aras et al., Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2, J Hum Genet, vol.62, issue.3, pp.447-51, 2016.

A. Jamsheer, E. M. Olech, K. Koz?owski, M. Niedziela, A. Sowi?ska-seidler et al., Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency, J Hum Genet. juill, vol.61, issue.7, pp.577-83, 2016.

C. Silveira, G. F. Leal, and D. P. Cavalcanti, Desbuquois dysplasia type II in a patient with a homozygous mutation in XYLT1 and new unusual findings, Am J Med Genet A, vol.170, issue.11, pp.3043-3050, 2016.

A. , A. Br, A. , and L. , Endoplasmic reticulum retention of xylosyltransferase 1 (XYLT1) mutants underlying Desbuquois dysplasia type II, Am J Med Genet A, 2017.

E. K. Mis, L. Kf, Y. Kong, N. B. Schwartz, M. Domowicz et al., Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length, Dev Biol. 1 janv, vol.385, issue.1, pp.67-82, 2014.

M. Gosset, F. Berenbaum, S. Thirion, and C. Jacques, Primary culture and phenotyping of murine chondrocytes, Nat Protoc. août, vol.3, issue.8, pp.1253-60, 2008.

J. Jozefczuk, K. Drews, and J. Adjaye, Preparation of mouse embryonic fibroblast cells suitable for culturing human embryonic and induced pluripotent stem cells, J Vis Exp JoVE. 21 juin, issue.64, 2012.

B. Turgeon and S. Meloche, Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases, Physiol Rev. janv, vol.89, issue.1, pp.1-26, 2009.

J. D. Green, V. Tollemar, M. Dougherty, Z. Yan, L. Yin et al., Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering, Genes Dis. déc, vol.2, issue.4, pp.307-334, 2015.

E. Kim, S. Cho, J. Shin, M. Lee, K. Kim et al., Ihh and Runx2/Runx3 Signaling Interact to Coordinate Early Chondrogenesis: A Mouse Model, vol.8, p.55296, 2013.

M. A. Davoli, L. Lamplugh, A. Beauchemin, K. Chan, S. Mordier et al., Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats aged 0-21 days. II. Two proteinases, gelatinase B and collagenase-3, are implicated in the lysis of collagen fibrils, Dev Dyn. sept, vol.222, issue.1, pp.71-88, 2001.

A. Spagnoli, L. O'rear, R. L. Chandler, F. Granero-molto, D. P. Mortlock et al., TGF-? signaling is essential for joint morphogenesis, J Cell Biol. 18 juin, vol.177, issue.6, pp.1105-1122, 2007.

V. E. Papaioannou and R. R. Behringer, Early Embryonic Lethality in Genetically Engineered Mice: Diagnosis and Phenotypic Analysis, Vet Pathol. 1 janv, vol.49, issue.1, pp.64-70, 2012.

J. M. Ward, S. A. Elmore, and J. F. Foley, Pathology Methods for the Evaluation of Embryonic and Perinatal Developmental Defects and Lethality in Genetically Engineered Mice, Vet Pathol. 1 janv, vol.49, issue.1, pp.71-84, 2012.

M. B. Goldring, K. Tsuchimochi, and K. Ijiri, The control of chondrogenesis, J Cell Biochem. 1 janv, vol.97, issue.1, pp.33-44, 2006.

H. Akiyama, Control of chondrogenesis by the transcription factor Sox9, Mod Rheumatol. juin, vol.18, issue.3, pp.213-222, 2008.

T. Kobayashi, PTHrP and Ihh in chondrocytes, vol.10, 2002.

B. St-jacques, M. Hammerschmidt, and A. P. Mcmahon, Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation, Genes Dev. 15 août, vol.13, issue.16, pp.2072-86, 1999.

H. Akiyama, Interactions between Sox9 and -catenin control chondrocyte differentiation, Genes Dev. 22 avr, vol.18, issue.9, pp.1072-87, 2004.

M. Cortes, A. T. Baria, and N. B. Schwartz, Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate, Development. 15 mai, vol.136, issue.10, pp.1697-706, 2009.

L. Koziel, M. Kunath, O. G. Kelly, and A. Vortkamp, Ext1-Dependent Heparan Sulfate Regulates the Range of Ihh Signaling during Endochondral Ossification, Dev Cell. juin, vol.6, issue.6, pp.801-814, 2004.

D. M. Ornitz, J. Xu, J. S. Colvin, D. G. Mcewen, and C. A. Macarthur, Receptor Specificity of the Fibroblast Growth Factor Family, vol.7, 1996.

A. Yayon, M. Klagsbrun, J. D. Esko, P. Leder, and D. M. Ornitz, Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor, Cell. févr, vol.64, issue.4, pp.841-849, 1991.

X. Zhang, O. A. Ibrahimi, S. K. Olsen, H. Umemori, M. Mohammadi et al., Receptor Specificity of the Fibroblast Growth Factor Family: THE COMPLETE MAMMALIAN FGF FAMILY, J Biol Chem. 9 juin, vol.281, issue.23, pp.15694-700, 2006.

K. Kita, T. Kimura, N. Nakamura, H. Yoshikawa, and T. Nakano, PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation, Genes Cells. août, vol.13, issue.8, pp.839-50, 2008.

Y. Xie, S. Zhou, H. Chen, X. Du, C. L. Research et al., Advances in fibroblast growth factor signaling in growth plate development and disorders, J Mol Endocrinol. août, vol.53, issue.1, pp.11-34, 2014.

F. Rousseau, J. Bonaventure, L. Legeai-mallet, A. Pelet, J. M. Rozet et al., Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia, Nature. 15 sept, vol.371, issue.6494, pp.252-256, 1994.

S. Murakami, M. Kan, W. L. Mckeehan, B. Crombrugghe, and . De, Up-regulation of the chondrogenic Sox9 gene by fibroblast growth factors is mediated by the mitogenactivated protein kinase pathway, Proc Natl Acad Sci. 1 févr, vol.97, issue.3, pp.1113-1121, 2000.

S. Provot, G. Nachtrab, J. Paruch, A. P. Chen, A. Silva et al., A-Raf and B-Raf Are Dispensable for Normal Endochondral Bone Development, and Parathyroid Hormone-Related Peptide Suppresses Extracellular Signal-Regulated Kinase Activation in Hypertrophic Chondrocytes, Mol Cell Biol. 1 janv, vol.28, issue.1, pp.344-57, 2008.

F. Beier, A. C. Taylor, and P. Luvalle, Raf signaling stimulates and represses the human collagen X promoter through distinguishable elements, J Cell Biochem. 15 mars, vol.72, issue.4, pp.549-57, 1999.

X. Wang, H. Y. Lin, E. Ng-eaton, J. Downward, H. F. Lodish et al., Expression cloning and characterization of the TGF-? type III receptor, Cell, vol.15, issue.4, pp.797-805, 1991.

E. Blitz, A. Sharir, H. Akiyama, and E. Zelzer, Tendon-bone attachment unit is formed modularly by a distinct pool of Scx-and Sox9-positive progenitors, Development. 1 juill, vol.140, issue.13, pp.2680-90, 2013.

P. Kannu, J. F. Bateman, S. Randle, S. Cowie, D. Du-sart et al., Premature arthritis is a distinct type II collagen phenotype, Arthritis Rheum. mai, vol.62, issue.5, pp.1421-1451, 2010.

I. Rukavina, G. Mortier, L. Van-laer, M. Frkovi?, T. ?api? et al., Mutation in the type II collagen gene (COL2AI) as a cause of primary osteoarthritis associated with mild spondyloepiphyseal involvement, Semin Arthritis Rheum. août, vol.44, issue.1, pp.101-105, 2014.

C. E. De-andrea, F. A. Prins, M. I. Wiweger, and P. C. Hogendoorn, Growth plate regulation and osteochondroma formation: insights from tracing proteoglycans in zebrafish models and human cartilage, J. Pathol, vol.224, pp.160-168, 2011.

K. Mythreye and G. C. Blobe, Proteoglycan Signaling Co-receptors: Roles in Cell Adhesion, Migration and Invasion, Cell. Signal, vol.21, pp.1548-1558, 2009.

D. Yan and X. Lin, Shaping morphogen gradients by proteoglycans, Cold Spring Harb. Perspect. Biol, vol.1, p.2493, 2009.

M. Cortes, A. T. Baria, and N. B. Schwartz, Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate, Dev. Camb. Engl, vol.136, pp.1697-1706, 2009.

R. V. Iozzo and L. Schaefer, Proteoglycan form and function: A comprehensive nomenclature of proteoglycans, Matrix Biol, vol.42, pp.11-55, 2015.

K. Prydz and K. T. Dalen, Synthesis and sorting of proteoglycans, J. Cell Sci, vol.113, pp.193-205

A. E. Kearns, S. C. Campbell, J. Westley, and N. B. Schwartz, Initiation of chondroitin sulfate biosynthesis: a kinetic analysis of UDP-D-xylose: core protein beta-D-xylosyltransferase, Biochemistry (Mosc.), vol.30, pp.7477-7483, 1991.

S. Schön, C. Prante, C. Bahr, J. Kuhn, K. Kleesiek et al., Cloning and recombinant expression of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II, J. Biol. Chem, vol.281, pp.14224-14231, 2006.

S. Müller, M. Schöttler, S. Schön, C. Prante, T. Brinkmann et al., Human xylosyltransferase I: functional and biochemical characterization of cysteine residues required for enzymic activity, Biochem. J, vol.386, pp.227-236, 2005.

N. Venkatesan, L. Barré, M. Bourhim, J. Magdalou, D. Mainard et al., Xylosyltransferase-I Regulates Glycosaminoglycan Synthesis during the Pathogenic Process of Human Osteoarthritis, PloS One, vol.7, pp.1-9, 2012.

M. Khair, M. Bourhim, L. Barré, D. Li, P. Netter et al., Regulation of xylosyltransferase I gene expression by interleukin 1? in human primary chondrocyte cells: mechanism and impact on proteoglycan synthesis, J. Biol. Chem, vol.288, pp.1774-1784, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01464669

F. Malfait, A. Kariminejad, T. Van-damme, C. Gauche, D. Syx et al., Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder, Am. J. Hum. Genet, vol.92, pp.935-945, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01451641

F. Cartault, P. Munier, M. L. Jacquemont, J. Vellayoudom, B. Doray et al., Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome, Eur. J. Hum. Genet. EJHG, vol.23, pp.49-53, 2015.

M. Nakajima, S. Mizumoto, N. Miyake, R. Kogawa, A. Iida et al., Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders, Am. J. Hum. Genet, vol.92, pp.927-934, 2013.

B. S. Budde, S. Mizumoto, R. Kogawa, C. Becker, J. Altmüller et al., Skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia is caused by a novel mutation in B3GAT3, Hum. Genet, vol.134, pp.691-704, 2015.

V. S. Salazar, L. W. Gamer, and V. Rosen, BMP signalling in skeletal development, disease and repair, Nat. Rev. Endocrinol, vol.12, pp.203-221, 2016.

E. B. Hunziker, Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes, Microsc. Res. Tech, vol.28, pp.505-519, 1994.

H. Kresse and E. Schönherr, Proteoglycans of the extracellular matrix and growth control, J. Cell. Physiol, vol.189, pp.266-274, 2001.

A. Aszodi, E. B. Hunziker, C. Brakebusch, and R. Fässler, Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis, Genes Dev, vol.17, pp.2465-2479, 2003.

Y. Tamamura, T. Otani, N. Kanatani, E. Koyama, J. Kitagaki et al., Developmental Regulation of Wnt/Beta-Catenin Signals Is Required for Growth Plate Assembly, Cartilage Integrity, and Endochondral Ossification, The Journal of Biological Chemistry, vol.280, pp.19185-19195, 2005.

C. Prein, N. Warmbold, Z. Farkas, M. Schieker, A. Aszodi et al., Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy, Matrix Biol, vol.50, pp.1-15, 2016.

L. Macri, D. Silverstein, and R. A. Clark, Growth factor binding to the pericellular matrix and its importance in tissue engineering, Adv. Drug Deliv. Rev, vol.59, pp.1366-1381, 2007.

J. F. Bateman, R. P. Boot-handford, and S. R. Lamandé, Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations, Nat. Rev. Genet, vol.10, pp.173-183, 2009.

N. K. Al-jezawi, B. R. Ali, A. , and L. , Endoplasmic reticulum retention of xylosyltransferase 1 (XYLT1) mutants underlying Desbuquois dysplasia type II, Am. J. Med. Genet. A, vol.999, pp.1-9, 2017.

C. Silveira, G. F. Leal, and D. P. Cavalcanti, Desbuquois dysplasia type II in a patient with a homozygous mutation in XYLT1 and new unusual findings, Am. J. Med. Genet. A, vol.170, pp.3043-3047, 2016.

A. Jamsheer, E. M. Olech, K. Koz?owski, M. Niedziela, A. Sowi?ska-seidler et al., Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency, J. Hum. Genet, vol.61, pp.577-583, 2016.

C. Bui, C. Huber, B. Tuysuz, Y. Alanay, C. Bole-feysot et al., XYLT1 Mutations in Desbuquois Dysplasia Type 2, Am. J. Hum. Genet, vol.94, pp.405-414, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01704452

J. Schreml, B. Durmaz, O. Cogulu, K. Keupp, F. Beleggia et al., The missing 'link': an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation, Hum. Genet, vol.133, pp.29-39, 2013.

L. Faivre, V. Cormier-daire, A. M. Eliott, F. Field, A. Munnich et al., Desbuquois dysplasia, a reevaluation with abnormal and 'normal' hands: radiographic manifestations, Am. J. Med. Genet. A, vol.124, pp.48-53, 2004.

H. H. Lee and R. R. Behringer, Conditional Expression of Wnt4 during Chondrogenesis Leads to Dwarfism in Mice, PLoS ONE, vol.2, p.450, 2007.

J. Yang, P. Andre, L. Ye, and Y. Z. Yang, The Hedgehog signalling pathway in bone formation, Int. J. Oral Sci, vol.7, pp.73-79, 2015.

C. Hartmann and C. J. Tabin, Dual roles of Wnt signaling during chondrogenesis in the chicken limb, Dev. Camb. Engl, vol.127, pp.3141-3159, 2012.

R. J. Linhardt and T. Toida, Role of glycosaminoglycans in cellular communication, Acc. Chem. Res, vol.37, pp.431-438, 2004.

M. J. Hilton, L. Gutiérrez, D. A. Martinez, and D. E. Wells, EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development, Bone, vol.36, pp.379-386, 2005.

M. S. Domowicz, M. Cortes, J. G. Henry, and N. B. Schwartz, Aggrecan modulation of growth plate morphogenesis, Dev. Biol, vol.329, pp.242-257, 2008.

Y. Watanabe, K. Takeuchi, S. Higa-onaga, M. Sato, M. Tsujita et al., Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development, Biochem. J, vol.432, pp.47-55, 2010.

D. G. Wilson, K. Phamluong, W. Y. Lin, K. Barck, R. A. Carano et al., Chondroitin sulfate synthase 1 (Chsy1) is required for bone development and digit patterning, Dev. Biol, vol.363, pp.413-425, 2012.

L. Guo, N. H. Elcioglu, A. Iida, Y. K. Demirkol, S. Aras et al., Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2, J. Hum. Genet, vol.62, pp.447-451, 2017.

L. Faivre, M. Le-merrer, L. I. Al-gazali, M. G. Ausems, P. Bitoun et al., Homozygosity mapping of a Desbuquois dysplasia locus to chromosome 17q25.3, J. Med. Genet, vol.40, pp.282-284, 2003.

G. Karsenty and E. F. Wagner, Reaching a genetic and molecular understanding of skeletal development, Dev. Cell, vol.2, pp.389-406, 2002.

L. Shum, C. M. Coleman, Y. Hatakeyama, and R. S. Tuan, Morphogenesis and dysmorphogenesis of the appendicular skeleton, Birth Defects Res. Part C Embryo Today Rev, vol.69, pp.102-122, 2003.

O. Barbieri, S. Astigiano, M. Morini, S. Tavella, A. Schito et al., Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation, Am. J. Physiol. Cell Physiol, vol.285, pp.1504-1512, 2003.

C. C. Banos, A. H. Thomas, and C. K. Kuo, Collagen fibrillogenesis in tendon development: current models and regulation of fibril assembly, Birth Defects Res. Part C Embryo Today Rev, vol.84, pp.228-244, 2008.

G. Zhang, Y. Ezura, I. Chervoneva, P. S. Robinson, D. P. Beason et al., Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development, J. Cell. Biochem, vol.98, pp.1436-1449, 2006.

S. P. Reese, C. J. Underwood, and J. A. Weiss, Effects of decorin proteoglycan on fibrillogenesis, ultrastructure, and mechanics of type I collagen gels, Matrix Biol. J. Int. Soc. Matrix Biol, vol.32, pp.414-423, 2013.

B. F. Eames, Y. L. Yan, M. E. Swartz, D. S. Levic, E. W. Knapik et al., Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation, PLoS Genet, vol.7, p.1002246, 2011.

E. K. Mis, K. F. Liem, Y. Kong, N. B. Schwartz, M. Domowicz et al., Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length, Dev. Biol, vol.385, pp.67-82, 2014.

Z. Xie, M. Khair, I. Shaukat, P. Netter, D. Mainard et al., Noncanonical Wnt induces chondrocyte de-differentiation through Frizzled 6 and DVL-2/Braf/CaMKII?/syndecan 4 axis, Cell Death Differ, vol.25, p.1442, 2018.

T. Saitou, H. Kiyomatsu, and T. Imamura, Quantitative Morphometry for Osteochondral Tissues Using Second Harmonic Generation Microscopy and Image Texture Information, Sci. Rep, vol.8, p.2826, 2018.

K. A. Staines, V. E. Macrae, and C. Farquharson, The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling, J. Endocrinol, vol.214, pp.241-255, 2012.

, This model was generated by deletion 10.5 kb (promoter and exon1) in Xylt1 gene by homologous recombination. To obtain XT-I KO mice we have crossed XT-I heterozygote females and XT-I heterozygote males and

, For genotyping of littermates, genomic DNA was extracted from the tail shippets using two solution of extraction buffer (solution 1: 25mM NaOH, 0,2mM NA2EDTA ph12, solution 2: 40mM Tris-HCL ph5). Genotyping was performed according to

. Souris, Ef/Wr for the 5' part of target locus of the wild type allele (Ef: 5'ctcattccatggtgaacacggg 3', Wr: 3'gctcttcattcattcacatgtcctcatcacc 5'), Ef2/Lxr for Loxp specific sequences (Ef2:5'acagaatttgcagcatatcaacatgatc 3', Lxr: 3'gaagttatactgagcggccgttcac 5'). The results were interpreted according of the size of the PCR product. XT-I KO (364 pb), XT-I WT (404 pb) and XT-I heterozygote

, Embryos were dissected and fixed overnight in 96% ethanol. Cartilage elements of skeletons were stained in 0.03% Alcian Blue dye (0.03g Alcian Blue (8GX, Sigma) dissolved in 80 ml 95% ethanol and 20 ml glacial acetic acid). Skeletons were washed twice with 95% ethanol and then

, Bones/mineralized tissues were stained in 2% Alizarin Red (100 ml 1% KOH, 0,02% Alizarin Red (Sigma)) for 4h and cleared in 0,8% KOH in 20% glycerol solution for 24h

, KOH glycerol solution for 48h. Finally, embryonic skeletons were stored in a 50% glycerol, 50% ethanol solution

, Their limbs were dissected independently of each other and were fixed at room temperature for 24h in 10% formalin. Then, they were dehydrated with a series of ethanol baths (70%, 90%, 100%) and then passed through a toluene bath before they were embedded in paraffin. Sections of 5?m sections were cut using the Leica microtome and stained with Blue Alcian (Sigma), Histological analysis and staining XT-I KO embryos and their wild littermates were collected at different embryonic stages at E14.5, E16.5 and E18.5

H. Muir, Proteoglycans of cartilage, p.15

L. Kjellen, Proteoglycans: Structures and Interactions, p.33

J. R. Couchman, Transmembrane Signaling Proteoglycans, Annu. Rev. Cell Dev. Biol, vol.26, pp.89-114, 2010.

R. V. Iozzo and L. Schaefer, Proteoglycan form and function: A comprehensive nomenclature of proteoglycans, Matrix Biol, vol.42, pp.11-55, 2015.

K. Prydz and K. T. Dalen, Synthesis and sorting of proteoglycans

C. B. Knudson, G. A. Nofal, L. Pamintuan, and D. J. Aguiar, The chondrocyte pericellular matrix: a model for hyaluronan-mediated cell-matrix interactions, Biochem. Soc. Trans, vol.27, pp.142-147, 1999.

J. Melrose, C. Shu, J. M. Whitelock, and M. S. Lord, The cartilage extracellular matrix as a transient developmental scaffold for growth plate maturation, Matrix Biol, pp.363-383, 2016.

F. P. Rojas, Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules, Biomacromolecules, vol.15, pp.772-780, 2014.

R. Sasisekharan, Z. Shriver, G. Venkataraman, and U. Narayanasami, Roles of heparansulphate glycosaminoglycans in cancer, Nat. Rev. Cancer, vol.2, pp.521-528, 2002.

T. N. Wight and M. J. Merrilees, Proteoglycans in atherosclerosis and restenosis: key roles for versican, Circ. Res, vol.94, pp.1158-1167, 2004.

J. Van-horssen, P. Wesseling, L. P. Van-den-heuvel, R. M. De-waal, and M. M. Verbeek, Heparan sulphate proteoglycans in Alzheimer's disease and amyloid-related disorders, Lancet Neurol, vol.2, pp.482-492, 2003.

S. Hashimoto, Chondrocyte-derived apoptotic bodies and calcification of articular cartilage, Proc. Natl. Acad. Sci, vol.95, pp.3094-3099, 1998.

N. B. Schwartz and M. Domowicz, Chondrodysplasias due to proteoglycan defects, Glycobiology, vol.12, pp.57-68, 2002.

B. K. Hall and T. Miyake, The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis, Anat. Embryol. (Berl.), vol.186, 1992.

B. R. Olsen, A. M. Reginato, W. Wang, . Bone, and . Development, , p.32, 2000.

F. Long and D. M. Ornitz, Development of the Endochondral Skeleton, Cold Spring Harb. Perspect. Biol, vol.5, pp.8334-008334, 2013.

H. M. Kronenberg, Developmental regulation of the growth plate, Nature, vol.423, pp.332-336, 2003.

M. B. Goldring, K. Tsuchimochi, and K. Ijiri, The control of chondrogenesis, J. Cell. Biochem, vol.97, pp.33-44, 2006.

E. Kozhemyakina, A. B. Lassar, and E. Zelzer, A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation, Development, vol.142, pp.817-831, 2015.

B. F. Eames, Mutations in fam20b and xylt1 Reveal That Cartilage Matrix Controls Timing of Endochondral Ossification by Inhibiting Chondrocyte Maturation, PLoS Genet, vol.7, p.1002246, 2011.

. Schreml, The missing 'link': an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation, Hum. Genet, vol.133, pp.29-39, 2014.

C. Bui, XYLT1 mutations in Desbuquois dysplasia type 2, Am. J. Hum. Genet, vol.94, pp.405-414, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01704452

S. Van-koningsbruggen, Complete and partial XYLT1 deletion in a patient with neonatal short limb skeletal dysplasia, Am. J. Med. Genet. A, vol.170, pp.510-514, 2016.

A. Jamsheer, Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency, J. Hum. Genet, vol.61, pp.577-583, 2015.

C. Silveira, G. F. Leal, and D. P. Cavalcanti, Desbuquois dysplasia type II in a patient with a homozygous mutation in XYLT1 and new unusual findings, Am. J. Med. Genet. A, vol.170, pp.3043-3047, 2016.

L. Guo, Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2, J. Hum. Genet, vol.62, pp.447-451, 2017.

N. K. Al-jezawi, B. R. Ali, and L. Al-gazali, Endoplasmic reticulum retention of xylosyltransferase 1 (XYLT1) mutants underlying Desbuquois dysplasia type II, Am. J. Med. Genet. A, 2017.

B. Turgeon and S. Meloche, Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases, Physiol. Rev, vol.89, pp.1-26, 2009.

V. E. Papaioannou and R. R. Behringer, Early Embryonic Lethality in Genetically Engineered Mice: Diagnosis and Phenotypic Analysis, Vet. Pathol, vol.49, pp.64-70, 2012.

J. M. Ward, S. A. Elmore, and J. F. Foley, Pathology Methods for the Evaluation of Embryonic and Perinatal Developmental Defects and Lethality in Genetically Engineered Mice, Vet. Pathol, vol.49, pp.71-84, 2012.

E. K. Mis, Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length, Dev. Biol, vol.385, pp.67-82, 2014.

C. Götting, J. Kuhn, R. Zahn, T. Brinkmann, and K. Kleesiek, Molecular Cloning and Expression of Human UDP-d-Xylose: Proteoglycan Core Protein ?-dXylosyltransferase and its First Isoform XT-II, J. Mol. Biol, vol.304, pp.517-528, 2000.

E. Condac, Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating enzyme of glycosaminoglycan biosynthesis, Proc. Natl. Acad. Sci, vol.104, pp.9416-9421, 2007.

B. De-crombrugghe, V. Lefebvre, and K. Nakashima, Regulatory mechanisms in the pathways of cartilage and bone formation, Curr. Opin. Cell Biol, vol.13, pp.721-728, 2001.

H. Akiyama, The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6, Genes Dev, vol.16, pp.2813-2828, 2002.

P. Dy, Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes, Dev. Cell, vol.22, pp.597-609, 2012.

J. D. Green, Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering, Genes Dis, vol.2, pp.307-327, 2015.

A. Vortkamp, Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein, Science, vol.273, pp.613-622, 1996.

. Long, Direct requirement for Ihh signaling in chondrocyte proliferation, vol.10, 2001.

E. Kim, Ihh and Runx2/Runx3 Signaling Interact to Coordinate Early Chondrogenesis: A Mouse Model, PLoS ONE, vol.8, p.55296, 2013.

M. A. Davoli, Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats aged 0-21 days. II. Two proteinases, gelatinase B and collagenase-3, are implicated in the lysis of collagen fibrils, Dev. Dyn, vol.222, pp.71-88, 2001.

E. R. Lee, Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats ages 0-21 days: I. Two groups of proteinases cleave the core protein of aggrecan, Dev. Dyn, vol.222, pp.52-70, 2001.

D. M. Ornitz, FGF signaling in the developing endochondral skeleton, Cytokine Growth Factor Rev, vol.16, pp.205-213, 2005.

Y. Xie, S. Zhou, H. Chen, X. Du, L. Chen et al., Advances in fibroblast growth factor signaling in growth plate development and disorders, J. Mol. Endocrinol, vol.53, pp.11-34, 2014.

F. Rousseau, Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia, Nature, vol.371, pp.252-254, 1994.

E. Minina, C. Kreschel, M. C. Naski, D. M. Ornitz, and A. Vortkamp, Interaction of FGF, Ihh/Pthlh, and BMP Signaling Integrates Chondrocyte Proliferation and Hypertrophic Differentiation, Dev. Cell, vol.3, pp.439-449, 2002.

L. Dailey, D. Ambrosetti, A. Mansukhani, and C. Basilico, Mechanisms underlying differential responses to FGF signaling, Cytokine Growth Factor Rev, vol.16, pp.233-247, 2005.

M. A. Cleary, G. J. Van-osch, P. A. Brama, C. A. Hellingman, R. Narcisi et al., embryonic to in vitro cartilage development from mesenchymal stem cells, J. Tissue Eng. Regen. Med, vol.9, pp.332-342, 2015.

H. Seo and R. Serra, Deletion of Tgfbr2 in Prx1-cre expressing mesenchyme results in defects in development of the long bones and joints, Dev. Biol, vol.310, pp.304-316, 2007.

A. Spagnoli, TGF-? signaling is essential for joint morphogenesis, J. Cell Biol, vol.177, pp.1105-1117, 2007.

W. Bi, J. M. Deng, Z. Zhang, R. R. Behringer, and B. De-crombrugghe, Sox9 is required for cartilage formation, Nat. Genet, vol.22, pp.85-89, 1999.

T. Hattori, SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification, Development, vol.137, pp.901-911, 2010.

H. Akiyama, Control of chondrogenesis by the transcription factor Sox9, Mod. Rheumatol, vol.18, pp.213-219, 2008.

D. M. Bell, SOX9 directly regulates the type-II collagen gene, Nat. Genet, vol.16, pp.174-178, 1997.

B. St-jacques, M. Hammerschmidt, and A. P. Mcmahon, Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation, Genes Dev, vol.13, pp.2072-2086, 1999.

T. Kobayashi, PTHrP and Ihh in chondrocytes

F. Long, Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton, Development, vol.131, pp.1309-1318, 2004.

H. Akiyama, Interactions between Sox9 and -catenin control chondrocyte differentiation, Genes Dev, vol.18, pp.1072-1087, 2004.

T. Komori, Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts, Cell, vol.89, pp.755-764, 1997.

C. A. Yoshida, Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog, Genes Dev, vol.18, pp.952-963, 2004.

F. Otto, Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development, Cell, vol.89, pp.765-771, 1997.

M. Inada, Maturational disturbance of chondrocytes inCbfa1-deficient mice, Dev. Dyn, vol.214, pp.279-290, 1999.

D. M. Ornitz and N. Itoh, The Fibroblast Growth Factor signaling pathway, Wiley Interdiscip. Rev. Dev. Biol, vol.4, pp.215-266, 2015.

C. Li, A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors, Hum. Mol. Genet, vol.8, pp.35-44, 1999.

S. Murakami, Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype, Genes Dev, vol.18, pp.290-305, 2004.

P. Krejci, Bisindolylmaleimide I Suppresses Fibroblast Growth Factor-mediated Activation of Erk MAP Kinase in Chondrocytes by Preventing Shp2 Association with the Frs2 and Gab1 Adaptor Proteins, J. Biol. Chem, vol.282, pp.2929-2936, 2007.

S. Murakami, M. Kan, W. L. Mckeehan, B. Crombrugghe, and . De, Up-regulation of the chondrogenic Sox9 gene by fibroblast growth factors is mediated by the mitogenactivated protein kinase pathway, Proc. Natl. Acad. Sci, vol.97, pp.1113-1118, 2000.

S. Provot, A-Raf and B-Raf Are Dispensable for Normal Endochondral Bone Development, and Parathyroid Hormone-Related Peptide Suppresses Extracellular Signal-Regulated Kinase Activation in Hypertrophic Chondrocytes, Mol. Cell. Biol, vol.28, pp.344-357, 2008.

F. Beier, A. C. Taylor, and P. Luvalle, Raf signaling stimulates and represses the human collagen X promoter through distinguishable elements, J. Cell. Biochem, vol.72, pp.549-557, 1999.

C. Oh, Opposing Role of Mitogen-activated Protein Kinase Subtypes, Erk-1/2 and p38, in the Regulation of Chondrogenesis of Mesenchymes, J. Biol. Chem, vol.275, pp.5613-5619, 2000.

M. Cortes, A. T. Baria, and N. B. Schwartz, Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate, Development, vol.136, pp.1697-1706, 2009.

L. Koziel, M. Kunath, O. G. Kelly, and A. Vortkamp, Ext1-Dependent Heparan Sulfate Regulates the Range of Ihh Signaling during Endochondral Ossification, Dev. Cell, vol.6, pp.801-813, 2004.

X. Lin, Functions of heparan sulfate proteoglycans in cell signaling during development, Development, vol.131, pp.6009-6021, 2004.

A. Yayon, M. Klagsbrun, J. D. Esko, P. Leder, and D. M. Ornitz, Cell surface, heparinlike molecules are required for binding of basic fibroblast growth factor to its high affinity receptor, Cell, vol.64, pp.841-848, 1991.

D. M. Ornitz, J. Xu, J. S. Colvin, D. G. Mcewen, and C. A. Macarthur, Receptor Specificity of the Fibroblast Growth Factor Family, vol.7, 1996.

X. Zhang, Receptor Specificity of the Fibroblast Growth Factor Family: THE COMPLETE MAMMALIAN FGF FAMILY, J. Biol. Chem, vol.281, pp.15694-15700, 2006.

D. M. Ornitz, FGFs, heparan sulfate and FGFRs: complex interactions essential for development, BioEssays, vol.22, pp.108-112, 2000.

R. Priore, L. Dailey, and C. Basilico, Downregulation of Akt activity contributes to the growth arrest induced by FGF in chondrocytes, J. Cell. Physiol, vol.207, pp.800-808, 2006.

K. Kita, T. Kimura, N. Nakamura, H. Yoshikawa, and T. Nakano, Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation, Genes Cells, vol.13, pp.839-850, 2008.

F. López-casillas, Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system, Cell, vol.67, pp.785-795, 1991.

X. Wang, Expression cloning and characterization of the TGF-? type III receptor, Cell, vol.67, pp.797-805, 1991.