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

Abstract

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.