Orthosilicic acid Inhibits RANKL-Induced Osteoclastogenesis and Reverses Ovariectomy-Induced Bone Loss in Vivo

Silicon is essential for bone formation. Numerous experiments in vitro and in vivo have shown that an appropriate increase intake of silicon can facilitate the synthesis of collagen and its stabilization, and promote the differentiation and mineralization of osteoblasts. However, its effect on osteoclast-associated osteoporosis and the underlying mechanisms remain unclear. In this study, we examined whether orthosilicic acid restrain the differentiation of osteoclast through the receptor activator of nuclear factor κB ligand (RANKL)/ receptor activator of nuclear factor κB (RANK)/ osteoprotegerin(OPG) signaling pathway by investigating its effect in vitro and in vivo. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that orthosilicic acid inhibited osteoclast differentiation and RANKL-induced osteoclast marker gene and protein expression including c-Fos, nuclear factor of activated T cells cl (NFATcl), tumor necrosis factor receptor-associated factor 6(TRAF6), nuclear factor kappa B P50(NF- κB P50), NF- κB P52, RANK, Integrin β3, cathepsin K(CTSK). And we treated ovariectomized (OVX) mice with orthosilicic acid and revealed a protective effect of orthosilicic acid on osteoporosis in vivo. In conclusion, our finding demonstrated that orthosilicic acid suppresses RANKL-induced osteoclastogenesis and has potential value as a therapeutic agent for OVX-induced bone loss.