Superficial Zone Chondrocytes Modulate Polyphosphate Levels In Deep Zone Cartilage Which Correlate with Increased Tissue Formation And Decreased Mineralization By Deep Zone Chondrocytes

Loss of the superficial zone of articular cartilage is an early change in osteoarthritis and with disease progression the deep zone (DZ) of cartilage shows progressive mineralization. To date, the mechanism(s) regulating post-natal articular cartilage mineralization is poorly understood. Previously, we have shown that inorganic polyphosphate inhibits mineralization of in vitro-formed DZ cartilage. We developed an indirect co-culture method to investigate the effect of superficial zone chondrocytes (SZC) on mineralization in DZ cartilage. Our findings suggest that SZC suppress mineralization by modulating polyphosphate levels in DZ cartilage via FGF-18. Furthermore, SZC promote glycosaminoglycan and collagen accumulation in the extracellular matrix of cartilage formed by DZ chondrocytes. This study provides insight into the interaction between chondrocyte subpopulations and possible mechanism(s) controlling post-natal articular cartilage mineralization. Moreover, the results of this study establish polyphosphate and FGF-18, separately or in combination, as therapeutic candidates for articular cartilage repair and osteoarthritis prevention.MAS