Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation

Abstract

Osteoarthritis (OA) is a degenerative joint disease that is characterized by localized inflammatory and secondary proliferative changes. Suppressor of cytokine signaling 3 (SOCS3) is elevated during OA development. We investigated the effects of this protein on human chondrocyte survival in OA and the inflammatory response together with the mechanisms of these effects. Small interfering RNA (siRNA) was used to knock down the expression of SOCS3 in interleukin(IL)-1β-induced primary human osteoarthritic chondrocytes. We found that siRNA-mediated SOCS3 knock-down in human osteoarthritic chondrocytes increased production of IL-1β-induced prostaglandin E2, cell growth, transcript level and nuclear translocation of cyclin D1. Silencing of SOCS3 resulted in altered expression of nuclear factor-kappa-B (NF-κB) and cyclooxygenase (COX2). Our findings indicate that enhanced SOCS3 could have contradictory influences on OA development. SOCS3 might protect damaged joints by its anti-inflammatory effect and by inhibition of over-augmented cartilage tissue repair, which could exhibit inhibitory properties for joint inflammation, abnormal chondrocyte clustering and osteophyte formation in OA. On the other hand, SOCS3 might reduce chondrocyte growth response, which would delay repair of subchondral cancellous bone damage in OA owing to its anti-proliferation effect. The anti-inflammation and growth inhibition effects exhibited by enhanced SOCS3 in OA appear to be related to its capacity to down-regulate expression levels of NF-κB and COX2.