An Update on the Emerging Role of Resistin on the Pathogenesis of Osteoarthritis

Abstract

Background: Resistin may be involved in the pathogenesis of osteoarthritis (OA), but a systematic understanding of the role of resistin in OA is lacking.

Methods: We reviewed studies that evaluated the role of resistin in OA. The expression levels of resistin in vitro experiments and OA/rheumatoid arthritis (RA) patients were analyzed. We also studied potential resistin receptors and the signaling pathways that these receptors activate, ultimately leading to cartilage degeneration.

Results: Resistin levels in both the serum and synovial fluid were higher in OA and RA patients than in healthy subjects. Overall, resistin levels are much higher in serum than in synovial fluid. In human cartilage, resistin induces the expression of proinflammatory factors such as degradative enzymes, leading to the inhibition of cartilage matrix synthesis, perhaps by binding to Toll-like receptor 4 and the adenylyl cyclase-associated protein 1 receptor, which then activates the p38-mitogen-activated phosphate kinase, protein kinase A-cyclic AMP, nuclear factor-κB, and C/enhancer-binding protein β signaling pathways.

Conclusion: Resistin levels are higher in OA patients than in healthy controls; however, the precise role of resistin in the pathogenesis of OA needs to be studied further. Resistin may be a novel therapeutic target in OA in the future.

Figure 1

The potential proinflammatory role of resistin in the pathogenesis of osteoarthritis. Resistin possibly binds to the transmembrane Toll-like receptor 4 (TLR4) and activates TNF receptor-associated factor 6 (TRAF6) through the MyD88-dependent signaling pathway, which then activates the p38-mitogen-activated protein kinase (MAPK), C/enhancer-binding protein β (EBPβ), and nuclear factor- (NF-) κB signaling pathways, leading to the activation of the transcription of proinflammatory cytokine genes in the cell nucleus. Resistin can also stimulate the expression of proinflammatory cytokines and chemokines through the p38-MAPK and NF-κB pathways by binding to adenylyl cyclase-associated protein 1 (CAP1) receptors, which activates the cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway.