Department of Orthopedic Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China.
Department of Orthopedic Surgery, Liaocheng People's Hospital, Liaocheng, Shandong, China.
J Pharm Pharmacol. 2018 Jan;70(1):81-88. doi: 10.1111/jphp.12835. Epub 2017 Oct 10.
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.
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.
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.
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.
由于具有抗癌和抗炎特性，雷公藤红素引起了广泛的关注，研究表明雷公藤红素可负向调节基质细胞衍生因子-1（SDF-1）和受体 C-X-C 趋化因子受体 4（CXCR4）信号。本研究旨在探讨雷公藤红素在骨关节炎（OA）中的体内作用，并探讨其潜在的分子机制。
我们建立了单碘乙酸（MIA）诱导的大鼠 OA 模型，并评估了雷公藤红素治疗对关节疼痛和软骨损伤的影响。我们进一步评估了 SDF-1/CXCR4 通路和软骨特异性基因在 mRNA 和蛋白水平的变化。
雷公藤红素显著减轻了 MIA 诱导的 OA 大鼠的关节疼痛和软骨损伤，并抑制了 MIA 注射引起的 SDF-1/CXCR4 及相关基因的上调。此外，MIA 诱导的软骨特异性基因减少也被雷公藤红素治疗所预防。
雷公藤红素可改善体内 OA，这可通过减轻 MIA 处理的 OA 大鼠的关节疼痛和减少软骨损伤来证明，这种作用是通过抑制 SDF-1/CXCR4 通路来介导的。
