Cyasterone inhibits IL-1?-mediated apoptosis and inflammation via the NF-?B and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritis in vivo

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degrad-ation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation -related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1/I and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and re-strained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1/I in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of os-teoarthritis potentially by regulating the nuclear factor kappa B (NF -KB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monoso-dium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for develop-ing cyasterone as an effective agent for the alleviation of osteoarthritis.