J. Pelletier, J. Martel-pelletier, and D. S. Howell, Etiopathogenesis of osteoarthritis, Arthritis and Allied Conditions: A Textbook of Rheumatology, p.1969, 1997.

J. A. Buckwalter and V. C. Mow, Cartilage repair in osteoarthritis In Osteoarthritis, Diagnosis and Medical/Surgical Management, p.71, 1992.

D. M. Mitrovic, M. Quintero, A. Stankovic, and A. Ruckeweart, Cell density of adult human femoral condylar articular cartilage: joints with normal and fibrillated surfaces, Lab. Invest, vol.49, p.309, 1983.

A. M. Bendele and S. L. White, Early Histopathologic and Ultrastructural Alterations in Femorotibial Joints of Partial Medial Meniscectomized Guinea Pigs, Veterinary Pathology, vol.36, issue.4, p.436, 1987.
DOI : 10.2106/00004623-196547030-00017

S. Hashimoto, R. L. Ochs, S. Komiya, and M. Lotz, Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis, Arthritis & Rheumatism, vol.388, issue.9, p.1632, 1998.
DOI : 10.1002/1529-0131(199809)41:9<1632::AID-ART14>3.0.CO;2-A

F. J. Blanco, R. Guitian, E. Vazquez-martul, F. J. De-toro, and F. Galdo, Osteoarthritis chondrocytes die by apoptosis: A possible pathway for osteoarthritis pathology, Arthritis & Rheumatism, vol.74, issue.2, p.284, 1998.
DOI : 10.1002/aja.1002030409

J. Stadler, M. Stefanovic-racic, T. R. Billiar, R. D. Curran, L. A. Mcintyre et al., Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide, J. Immunol, vol.147, p.3915, 1991.

A. J. Farrell, D. R. Blake, R. M. Palmer, and S. Moncada, Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases., Annals of the Rheumatic Diseases, vol.51, issue.11, p.1219, 1992.
DOI : 10.1136/ard.51.11.1219

I. B. Mcinnes, B. P. Leung, M. Field, X. Q. Wei, F. P. Huang et al., Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients, Journal of Experimental Medicine, vol.184, issue.4, p.1519, 1996.
DOI : 10.1084/jem.184.4.1519

G. A. Murrell, D. Jang, and R. J. Williams, Nitric Oxide Activates Metalloprotease Enzymes in Articular Cartilage, Biochemical and Biophysical Research Communications, vol.206, issue.1, p.15, 1995.
DOI : 10.1006/bbrc.1995.1003

D. Taskiran, M. Stefanovic-racic, H. Georgescu, and C. Evans, Nitric-Oxide Mediates Suppression of Cartilage Proteoglycan Synthesis by Interleukin-1, Biochemical and Biophysical Research Communications, vol.200, issue.1, p.142, 1994.
DOI : 10.1006/bbrc.1994.1426

J. Pelletier, D. V. Jovanovic, J. C. Fernandes, P. Manning, J. R. Connor et al., Reduced progression of experimental osteoarthritis in vivo by selective inhibition of inducible nitric oxide synthase, Arthritis & Rheumatism, vol.70, issue.7, p.1275, 1998.
DOI : 10.1172/JCI119280

J. Pelletier, D. V. Jovanovic, V. Lascau-coman, J. C. Fernandes, P. T. Manning et al., Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: Possible link with the reduction in chondrocyte apoptosis and caspase 3 level, Arthritis & Rheumatism, vol.43, issue.6, p.1290, 2000.
DOI : 10.1002/1529-0131(200006)43:6<1290::AID-ANR11>3.0.CO;2-R

S. Hashimoto, K. Takahashi, D. Amiel, R. D. Coutts, and M. Lotz, Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis, Arthritis & Rheumatism, vol.35, issue.7, p.1266, 1998.
DOI : 10.1083/jcb.41.1.59

F. J. Blanco, R. L. Ochs, H. Schwarz, and M. Lotz, Chondrocyte apoptosis induced by nitric oxide, Am. J. Pathol, vol.146, p.75, 1995.

R. Altman, E. Asch, D. Bloch, G. Bole, D. Borenstein et al., Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee, Arthritis & Rheumatism, vol.1, issue.8, p.1039, 1986.
DOI : 10.1002/art.1780290816

J. Martel-pelletier, R. Mccollum, N. Fujimoto, K. Obata, J. M. Cloutier et al., Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis, Lab. Invest, vol.70, p.807, 1994.

T. Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, Journal of Immunological Methods, vol.65, issue.1-2, p.55, 1983.
DOI : 10.1016/0022-1759(83)90303-4

W. C. Earnshaw, L. C. Martins, and S. H. Kaufmann, Mammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis, Annual Review of Biochemistry, vol.68, issue.1, p.383, 1999.
DOI : 10.1146/annurev.biochem.68.1.383

J. M. Adams and S. Cory, The Bcl-2 Protein Family: Arbiters of Cell Survival, Science, vol.281, issue.5381, p.1322, 1998.
DOI : 10.1126/science.281.5381.1322

D. J. Van-antwerp, S. J. Martin, I. M. Verma, and D. R. Green, Inhibition of TNF-induced apoptosis by NF-??B, Trends in Cell Biology, vol.8, issue.3, p.107, 1998.
DOI : 10.1016/S0962-8924(97)01215-4

Y. Lin, S. Y. Yao, R. A. Veach, T. R. Torgerson, and J. Hawiger, Inhibition of Nuclear Translocation of Transcription Factor NF-??B by a Synthetic Peptide Containing a Cell Membrane-permeable Motif and Nuclear Localization Sequence, Journal of Biological Chemistry, vol.263, issue.24, p.14255, 1995.
DOI : 10.1016/S0076-6879(83)96063-9

R. Schreck, D. N. Meier, W. Mannel, P. A. Droge, and . Baeuerle, Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells, Journal of Experimental Medicine, vol.175, issue.5, p.1181, 1992.
DOI : 10.1084/jem.175.5.1181

D. Salvemini, T. P. Misko, J. L. Masferrer, K. Seibert, M. G. Currie et al., Nitric oxide activates cyclooxygenase enzymes., Proc. Natl. Acad. Sci. USA 90, p.7240, 1993.
DOI : 10.1073/pnas.90.15.7240

D. Salvemini, P. T. Manning, B. S. Zweifel, K. Seibert, J. Connor et al., Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors., Journal of Clinical Investigation, vol.96, issue.1, p.301, 1995.
DOI : 10.1172/JCI118035

E. Bonfoco, D. Krainc, M. Anarcrona, P. Nicotera, and S. A. Lipton, Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures., Proc. Natl. Acad. Sci. USA 92, p.7162, 1995.
DOI : 10.1073/pnas.92.16.7162

G. Majno and I. Joris, Apoptosis, oncosis, and necrosis: an overview of cell death, Am. J. Pathol, vol.146, p.3, 1995.

A. V. Knethen and B. Brune, Cyclooxygenase-2: an essential regulator of NO-mediated apoptosis., The FASEB Journal, vol.11, issue.11, p.887, 1997.
DOI : 10.1096/fasebj.11.11.9285487

J. Stadler, B. G. Harbrecht, M. D. Silvio, R. D. Curran, M. L. Jordan et al., Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells, Journal of Leukocyte Biology, vol.53, issue.2, p.165, 1993.
DOI : 10.1002/jlb.53.2.165

Y. E. Henrotin, G. P. Zheng, A. H. Deby, J. M. Labasse, J. Y. Crielaard et al., Nitric oxide downregulates interleukin 1 (IL-1) stimulated IL-6, IL-8, and prostaglandin E 2 production by human chondrocytes, J. Rheumatol, vol.25, p.1595, 1998.

A. R. Amin, M. Attur, R. N. Patel, G. D. Thakker, P. J. Marshall et al., Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide., Journal of Clinical Investigation, vol.99, issue.6, p.1231, 1997.
DOI : 10.1172/JCI119280

Y. Geng, F. J. Blanco, M. Cornelisson, and M. Lotz, Regulation of cy- clooxygenase-2 expression in normal human articular chondrocytes, J. Immunol, vol.155, p.796, 1995.

C. G. Maloney, W. A. Kutchera, K. H. Albertine, T. M. Mcintyre, S. M. Prescott et al., Inflammatory agonists induce cyclooxygenase type 2 expression by human neutrophiles, J. Immunol, vol.160, p.1402, 1998.

F. J. Blanco and M. Lotz, IL-1-Induced Nitric Oxide Inhibits Chondrocyte Proliferation via PGE2, Experimental Cell Research, vol.218, issue.1, p.319, 1995.
DOI : 10.1006/excr.1995.1161

T. Shalom-barak, J. Quach, and M. Lotz, Interleukin-17-induced Gene Expression in Articular Chondrocytes Is Associated with Activation of Mitogen-activated Protein Kinases and NF-??B, Journal of Biological Chemistry, vol.157, issue.42, p.27467, 1998.
DOI : 10.1038/sj.onc.1201253

K. Subbaramaiah, W. J. Chung, and A. J. Dannenberg, Ceramide Regulates the Transcription of Cyclooxygenase-2, Journal of Biological Chemistry, vol.57, issue.49, p.32943, 1998.
DOI : 10.1074/jbc.273.34.21875

L. M. Landino, B. C. Crews, M. D. Timmons, J. D. Morrow, and L. J. Marnett, Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis, Proc. Natl. Acad. Sci. USA 93, p.15069, 1996.
DOI : 10.1111/j.1476-5381.1996.tb15475.x

G. M. Pasinetti and P. S. Aisen, Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain, Neuroscience, vol.87, issue.2, p.319, 1998.
DOI : 10.1016/S0306-4522(98)00218-8

L. Ho, H. Osaka, P. S. Aisen, and G. M. Pasinetti, Induction of cyclooxygenase (COX)-2 but not COX-1 gene expression in apoptotic cell death, Journal of Neuroimmunology, vol.89, issue.1-2, p.142, 1998.
DOI : 10.1016/S0165-5728(98)00132-5

L. J. Walton, I. J. Franklin, T. Bayston, L. C. Brown, R. M. Greenhalgh et al., Inhibition of Prostaglandin E2 Synthesis in Abdominal Aortic Aneurysms : Implications for Smooth Muscle Cell Viability, Inflammatory Processes, and the Expansion of Abdominal Aortic Aneurysms, Circulation, vol.100, issue.1, p.48, 1999.
DOI : 10.1161/01.CIR.100.1.48

C. S. Williams, M. Man, and R. N. Dubois, The role of cyclooxygenases in inflammation, cancer and development, Oncogene, vol.18, issue.55, p.7908, 1999.
DOI : 10.1074/jbc.274.38.27307

M. Tsujii and R. N. Dubois, Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2, Cell, vol.83, issue.3, p.493, 1995.
DOI : 10.1016/0092-8674(95)90127-2

T. A. Chan, P. J. Morin, B. Vogelstein, and K. W. Kinzler, Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis, Proc. Natl. Acad. Sci. USA 95, p.681, 1998.
DOI : 10.1007/BF00666099

T. Kawamori, C. V. Rao, K. Seibert, and B. S. Raddy, Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis, Cancer Res, vol.58, p.409, 1998.

M. Negishi, Y. Sugimoto, and A. Ichikawa, Prostaglandin E receptors, Journal of Lipid Mediators and Cell Signalling, vol.12, issue.2-3, p.379, 1995.
DOI : 10.1016/0929-7855(95)00024-K

M. Sabatini, G. Rolland, S. Leonce, M. Thomas, C. Lesur et al., Effects of Ceramide on Apoptosis, Proteoglycan Degradation, and Matrix Metalloproteinase Expression in Rabbit Articular Cartilage, Biochemical and Biophysical Research Communications, vol.267, issue.1, p.438, 2000.
DOI : 10.1006/bbrc.1999.1983

T. Nguyen, D. Brunson, C. L. Crespi, B. W. Penman, J. S. Wishnok et al., DNA damage and mutation in human cells exposed to nitric oxide in vitro., Proc. Natl. Acad. Sci. USA 89, p.3030, 1992.
DOI : 10.1073/pnas.89.7.3030

K. T. Lin, J. Y. Xue, M. Nomen, B. Spur, and P. Y. Wong, Peroxynitriteinduced apoptosis in HL-60 cells, J. Biol. Chem, vol.270, 1995.

M. Asahi, J. Fujii, K. Suzuki, H. G. Seo, T. Kuzuya et al., Inactivation of Glutathione Peroxidase by Nitric Oxide, Journal of Biological Chemistry, vol.269, issue.36, p.21035, 1995.
DOI : 10.1006/bbrc.1993.1246

D. E. Fisher, Apoptosis in cancer therapy: Crossing the threshold, Cell, vol.78, issue.4, p.539, 1994.
DOI : 10.1016/0092-8674(94)90518-5

T. Aizawa, S. Kokubun, T. Kawamata, Y. Tanaka, and H. I. Roach, c-Myc protein in the rabbit growth plate, The Journal of Bone and Joint Surgery, vol.81, issue.5, p.921, 1999.
DOI : 10.1302/0301-620X.81B5.9492

F. Pica, O. Franzese, C. D. Onofrio, E. Bonmassar, C. Favalli et al., Prostaglandin E2 induces apoptosis in resting immature and mature human lymphocytes: a c-Myc-dependent and Bcl-2-independent associated pathway, J. Pharmacol. Exp. Ther, vol.277, p.1793, 1996.

T. Kobayashi, K. Okamoto, T. Kobata, T. Hasunuma, T. Sumida et al., Tumor necrosis factor ? regulation of the Fas-mediated apoptosis-signaling pathway in synovial cells, Arthritis & Rheumatism, vol.27, issue.3, p.519, 1999.
DOI : 10.1002/eji.1830270523

M. Miwa, R. Saura, S. Hirata, Y. Hayashi, K. Mizuno et al., Induction of apoptosis in bovine articular chondrocyte by prostaglandin E2through cAMP-dependent pathway, Osteoarthritis and Cartilage, vol.8, issue.1, p.17, 2000.
DOI : 10.1053/joca.1999.0266

J. Pelletier, L. Viorica, D. Jovanovic, J. C. Fernandes, P. Manning et al., Selective inhibition of inducible nitric oxide synthase in experimental osteoarthritis is associated with reduction in tissue levels of catabolic factors, J. Rheumatol, vol.26, 1999.

K. Nishioka, T. Hasunuma, T. Kato, T. Sumida, and T. Kobata, Review: Apoptosis in rheumatoid arthritis: A novel pathway in the regulation of synovial tissue, Arthritis & Rheumatism, vol.350, issue.1, 1998.
DOI : 10.1002/1529-0131(199801)41:1<1::AID-ART1>3.0.CO;2-V