What are the molecular changes in OA causing pathogenesis?

Changes in cartilage matrix composition and properties (early disease water increases cause edema and softening, type II collagen synthesis decreases by MMP1&3, proteoglycan decrease, leads to increased water retention, accumulation of advanced glycation end products (AGE) lead to protein modification, bind to RAGE on chondrocytes leads to catabolic activity and more collagenase, leads to irreversible collagen damage) Changes in catabolism (MMP, matrix degrading enzymes, ADAMTS, aggrecanases) Activation of skeletal developmental pathways (TGFb, BMPs, Wnt signals, that stimulate chondrocyte hypertrophy, lead to osteophyte formation and fibrosis, activation and suppression of Wnt lead to OA.)