Pathophysiology of osteoarthritis
This theme is addressed through le role of microcrystals and bone tissue.
2. The presence of microcrystals of basic calcium phosphate (PCBs) in the articular cartilage correlates with cartilage destruction in osteoarthritis. Osteoarthritic cartilages contain consistently BCP crystals. Several types have been identified and are present diffusely in the cartilage of a joint osteoarthritis, including in areas that are macroscopically healthy areas of superficial and deep cartilage. The analysis threshold calcium showed that non-diffusible calcium ion was predominantly related to calcium crystals (Nguyen et al. Synchrotron Res 2011 J). In vitro, BCP crystals can induce cartilage damage by multiple mechanisms and are considered a real "stress microcrystalline" during osteoarthritis (Ea et al. Arthritis Rheum). These crystals can thus induce an inflammatory process by inducing the production of inflammatory cytokines by synoviocytes, a catabolic phenotype and apoptotic chondrocytes and production of metalloproteinases (Ea et al. Arthritis Rheum 2011). We characterized the signaling pathways induced by the crystals and the role of the inflammasome dependent or not IL-1.
2.1 It is obvious that the bone tissue plays an important role in the progression of osteoarthritis due to bone changes observed in patients and local tissue interactions. We use a murine model of joint instability induced by partial meniscectomy to analyze the impact of changes on the remodeling of cartilage metabolism. We have shown that bone tissue contributes to chondrolysis by activating catabolic mechanisms. In mice, the early stages of osteoarthritis are accompanied by an initial and transient bone resorption and are followed by a bone hyperformation (Kadri et al, Arthritis Rheum & 2008). Inhibition of bone resorption by a bisphosphonate reduces mechanically induced chondrolysis when there is a high bone turnover particularly in two mouse models with hyper-resorption: overexpression of Runx-2 specifically under the control of the promoter of collagen I (Kadri et al, Ann Rheum Dis 2010) or induced by ovariectomy (Funck-Brentano et al, PLoS ONE 2012). The anti-catabolic effects of inhibitors of bone resorption in cartilage are due to the decrease in the expression of matrix metalloproteases and reduced cleavage of aggrecan. This effect is mediated by factors produced by bone tissue as bisphosphonates have no impact on the in vitro production of proteoglycans. We have demonstrated that molecules secreted by bone cartilage catabolism induce a transfer of organotypic culture supernatants. Indeed, inhibition of bone resorption induced by bisphosphonates or estradiol in bone explants decreases aggrecan cleavage and the release of proteoglycans. There is a reversal of RANKL / OPG ratio in the subchondral bone in these models. Finally, in vitro blocking of OPG in bone explants increases the cleavage of aggrecan while OPG in vivo reduces the occurrence of OA, demonstrating that these factors of bone origin are able to regulate the balance of anabolism / catabolism in cartilage.