Salidroside and Apigenin attenuate bone resorption in ovariectomized mice and osteoclasts via Sema3A/Nrp1/PlexinA1 pathway.

Osteoporosis is becoming one of the major global health concerns with accelerating of the aging population and there is an urgent need for novel countermeasures. Salidroside (SAL) and Apigenin (AP) are compounds identified in Ligustri Lucidi Fructus (LLF), a dietary herb that has historically been used and is currently used in osteoporosis management. However, their effects on bone loss remain largely unexplored. To this end, ovariectomized (OVX) mice and osteoclasts differentiated from RAW 264.7 were used to establish the osteoporotic model in vivo and in vitro. We found that SAL and AP treatments reduce the numbers of TRAP-positive cells, F-actin rings and bone resorption pits, and suppress the expression levels of c-Fos, Nfatc1 and Ctsk in osteoclasts. In addition, SAL and AP can improve bone quality and decrease serum levels of CTX-1 and TRAP-5b in OVX mice. These compounds further increase the expression levels of Sema3A, Nrp1 and PlexinA1 in osteoclasts and osteoporotic animals. In conclusion, SAL and AP limit osteoclastic bone resorption to ameliorate bone quality via upregulation of the Sema3A/Nrp1/PlexinA1 signaling pathway, providing a novel strategy for osteoporosis management.