Cryptotanshinone inhibits osteoclast differentiation by targeting LCP1 to suppress diabetic osteoporosis

As a frequent complication of diabetes, diabetic osteoporosis (DOP) represents a growing clinical and public health challenge. The increased osteoclastogenesis in diabetic pathological states results in bone resorption and bone loss and the exacerbation of osteoporosis. Cryptotanshinone, a fat-soluble diterpenoid anthraquinone compound extracted from Salvia. miltiorrhiza Bge, has been demonstrated efficacy in the treatment of a variety of diseases. In this study, we present evidence that cryptotanshinone inhibits RANKL-induced osteoclast differentiation in a concentration-dependent manner in vitro. Furthermore, cryptotanshinone suppresses diabetic osteoporosis by inhibiting osteoclastogenesis in vivo. Mechanistically, cryptotanshinone binds to lymphocyte cytosolic protein 1 (LCP1) so that suppressing osteoclast fusion to reduce bone resorption. Collectively, these findings suggest that cryptotanshinone suppresses osteoclast differentiation and bone loss of DOP by targeting LCP1. Consequently, cryptotanshinone may represent a promising therapeutic agent for diabetic osteoporosis.