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Responsable : Christelle Sanchez

Osteoarthritis is a disease characterized by a progressive loss of articular cartilage. OA cartilage is characterized by fibrillations, fissures, vertical clefts, variable crystal deposition, and even in late stage of the disease disappearance of the full thickness surface of the joint.

Subchondral bone sclerosis

The disease processes not only affect the articular cartilage, but is accompanied by synovial membrane inflammation, osteophytes formation and subchondral bone thickening. This structural modification deeply modifies the mechanical properties of the subchondral bone, and subsequently increases mechanical strains applied on overlying cartilage. Both clinical and laboratory evidence indicates altered subchondral bone metabolism in OA, a situation that may results from abnormal osteoblast behaviour. Coupled with chemical/mechanical stresses, abnormal OA osteoblasts would then accelerate subchondral bone formation, which would enhance the mechanical pressure on the overlying cartilage in supporting joint, promoting cartilage deterioration. Indeed, osteoblasts isolated from the subchondral OA bone show an altered phenotype. In comparison with normal osteoblasts, they produce more insulin-like growth factor (IGF-1), transforming growth factor-beta (TGF-beta), hepatocyte growth factor (HGF), plasminogen activator (uPA), interleukin-6 (IL-6) and prostaglandin E2.
Recently, we have compared the phenotype of osteoblasts coming from sclerotic or non sclerotic areas of the osteoarthritic subchondral bone. The sclerotic osteoblasts produce more osteocalcin, osteopontin, IL-6, IL-8, expressed more ANKH and have an higher alkaline phosphatase and transglutaminase activity [1].

Bone/cartilage crosstalk

Herein, we hypothesize that OA osteoblasts could take part in cartilage breakdown. Since the presence of connections (microcracks, vascular channels, and neovascularization) between subchondral bone and cartilage has been demonstrated, it is speculated that mediators produced by subchondral osteoblasts could modulate chondrocyte metabolism and induce phenotype changes, particularly hypertrophic differenciation and cartilage matrix mineralization. In this purpose, we have developped a co-culture model in which chondrocytes and osteoblasts were cultured together. In this co-culture model, we have observed that sclerotic osteoblasts induced an increased of MMPs expression and a decreased of aggrecan and type II collagen expression by chondrocytes [2] [3].

Ahmed YA, Osteoarthritis Cart 2007

Mineralization of cartilage matrix

Hypertrophic differentiation of the chondrocytes proceeds physiologically within the cartilage growth plate. This process is characterized by the expression of genes encoding for hypertrophy-related molecules including type X collagen, alkaline phosphatase, Ihh, parathyroid hormone related protein (PTHrP). In this research programme, we aim to study the factors regulating the hypertrophic differentiation of chondrocytes.





[1] Sanchez C, Deberg M, Msika P, Delcour J, Bellahcene A, Castronovo V, Henrotin Y. Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritis subchondral bone. Arthritis Rheum 2008; 58 (2): 442-455. [Pubmed]
[2] Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JY, Henrotin YE. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthritis Cartilage 2005;13: 979-87. [Pubmed]
[3] Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JY, Henrotin YE. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2005;13: 988-97. [Pubmed]