Strontium ion attenuates osteoarthritis through inhibiting senescence and enhancing autophagy in fibroblast-like synoviocytes

Abstract

Abstract Osteoarthritis (OA) mainly occurs in the elderly population and seriously affects their quality of life. The strontium (Sr) ion has shown positive effects on the bone tissue and promises on OA treatment. However, the adequate treatment dosage and the underlying mechanisms are unclear. This study investigated the effect of different concentrations of Sr ion on a mouse model of OA induced by destabilization of the medial meniscus (DMM) surgery, as well as the underlying mechanisms. DMM-induced OA mice were received intra-articular injection different concentration Sr ion, and found a suitable concentration of Sr ion to improve OA. Furthermore, the mechanism by which Sr ion mediated senescence and autophagy of fibroblast-like synoviocytes (FLSs) in Synovial tissues of DMM-induced OA mice were investigated. In OA mice treated with 10 µl contained 5 mmol/L SrCl2 showed the best effect on improved the pain-related behaviors and cartilage damage. In addition, in vivo and vitro experiments revealed that Sr ion inhibits senescence and improves autophagy function of FLSs. We also found that enhancement of autophagy function of FLSs can effectively slow down itself senescence. Therefore, we show that Sr ions through AMPK/mTOR/LC3B-Ⅱ signal axis improves FLSs autophagy function and delays FLSs senescence, furthermore, improve OA. These results suggest that senescence and autophagy function of FLSs may serve as promising targets for OA treatment and Sr ion may inhibit OA progression through these two targets.