Celastrol attenuates pain and cartilage damage via SDF-1/CXCR4 signalling pathway in osteoarthritis rats

Abstract

OBJECTIVES: Celastrol has attracted wide interests for its anticancer and anti-inflammation properties, and studies have demonstrated that celastrol negatively modulates the stromal cell-derived factor-1 (SDF-1) and receptor C-X-C chemokine receptor type 4 (CXCR4) signalling. We aim in this study to investigate the effects of celastrol in osteoarthritis (OA) in vivo and explored the underlying molecular mechanisms. METHODS: We established a monoiodoacetate (MIA)-induced rat OA model and evaluated the joint pain and cartilage damage with or without celastrol treatments. We further assessed the alterations of the SDF-1/CXCR4 pathway and cartilage-specific genes, at both mRNA and protein levels. KEY FINDINGS: Celastrol significantly attenuated the joint pain and cartilage damage induced by MIA in OA rats and suppressed the upregulation of SDF-1/CXCR4 and associated genes caused by MIA injections. Furthermore, MIA induced a decrease in cartilage-specific genes which was also prevented by celastrol treatments. CONCLUSIONS: Celastrol ameliorate OA in vivo as evidenced by the attenuated joint pain and less cartilage damage in OA rats given celastrol treatments, an effect mediated via suppression of the SDF-1/CXCR4 pathway.