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Dysregulation and phenotypic modification of osteoarthritic osteoblast by Galectin-3: Identification of cellular ligands

Abstract : Osteoblasts are the main cells in subchondral bone (SCB), which are responsible for the bone matrix production. Their differentiation can be evaluated by type I collagen and alkaline phosphatase in the early stage and by osteocalcin (OCN) and mineralization in the late stage. Alterations of SCB are essential episodes of osteoarthritis (OA) and are represented by a significant bone formation accompanied with abnormal hypomineralization. These changes in SCB are related to phenotypic modifications of osteoblasts. Galectin-3 (Gal-3) is an inflammatory factor markedly detected in the synovial tissue and synovial fluid during OA inflammation. Previous studies have demonstrated that gal-3 was deleterious for cartilage and inhibited the production of OCN in OA osteoblasts. These findings suggest that gal-3 can participate in either the initiation or progression of osteoarthritis. So far, a few studies have been conducted to explore the role of Gal-3 in OA and particularly related to SCB. In this context, the thesis has consisted to characterize OA osteoblasts, to investigate the modulation of the OA osteoblast phenotype by gal-3 and finally to identify the involved cellular mechanisms. We have identified two populations of OA osteoblasts according to the OCN expression. Under basal conditions, these two populations express TGF-ß1, Wnt5b and DKK2 differentially, suggesting various differentiation and heterogeneous phenotype of osteoblasts in OA patients. Moreover, we confirmed the deleterious role of gal-3 in the joint during inflammation since it stimulates the production of collagenase 1 involved in bone degradation. In addition, it emphasizes the disruption of phenotypic osteoblasts by producing more leptin during hypoxic episodes. Although several membrane ligands can mediate the effects of gal-3, 4F2hc seems to play a prominent role
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Submitted on : Thursday, March 29, 2018 - 1:27:01 PM
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Yong Hu. Dysregulation and phenotypic modification of osteoarthritic osteoblast by Galectin-3: Identification of cellular ligands. Human health and pathology. Université de Lorraine, 2015. English. ⟨NNT : 2015LORR0101⟩. ⟨tel-01751798⟩



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