Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis

摘要: Objectives: Basic calcium phosphate (BCP) crystal and interleukin 6 (IL-6) have been implicated in osteoarthritis (OA). We hypothesise that these two factors may be linked a reciprocal amplification loop which leads to OA. Methods: Primary murine chondrocytes human cartilage explants were incubated with hydroxyapatite (HA) crystals, form of BCP, the modulation cytokines matrix-degrading enzymes assayed. The ability IL-6 stimulate chondrocyte calcification was assessed vitro. mechanisms underlying effects HA on investigated using chemical inhibitors, pathways mediating IL-6-induced characterised by quantifying expression genes involved mineralisation. role vivo studied meniscectomy model OA (MNX), link between degradation histology. Results: In chondrocytes, BCP crystals stimulated secretion, further amplified an autocrine loop, through signalling involving Syk PI3 kinases, Jak2 Stat3 molecules. Exogenous promoted calciumcontaining formation upregulation calcification: pyrophosphate channel Ank, Annexin5 sodium/ cotransporter Pit-1. Treatment inhibitors significantly inhibited formation. meniscectomised mice, increasing deposits observed around joint correlated expression. Finally, induced proteoglycan loss explants, reduced inhibitor. Conclusions:BCP positive feedback leading OA. Targeting and/or are promising therapeutic strategies