Lithium-containing biomaterials inhibit osteoclastogenesis of macrophagesin vitroand osteolysisin vivo

Osteolysis, which is caused by aging, neoplasia, infection, or trauma, is a type of intractable systemic or local syndrome of bone destruction (e.g., peri-implant osteolysis (PIO)). The activation of osteoclasts differentiated from macrophages plays a decisive role in such diseases. To conquer this challenge, herein, a biomaterial capable of inhibiting osteoclastogenesis and osteolysis was designed. Recent research has shown that lithium (Li) can inhibit pro-inflammatory cytokine release in vitro via affecting the pharmacotherapy of psychiatric illnesses. Therefore, we synthesized a pure-phase lithium-calcium-silicate (Li₂Ca₂Si₂O₇, LCS) bioceramic and further prepared extracts to assess the effect of LCS on RANKL-induced osteoclastogenesis in vitro and Ti particle-induced osteolysis in vivo as well as the corresponding mechanism. The results demonstrated that LCS inhibited RANKL-induced osteoclastogenesis of macrophages, bone resorption area, and F-actin ring formation in a dose-dependent manner. The mechanism is related to the suppression of the NF-kB signaling pathways mediating the inhibitory effects of LCS. Moreover, LCS was found to be able to inhibit calvarial osteolysis in a mouse model through micro-CT and histological analysis. These findings suggest that LCS may be a promising biomaterial for suppressing osteolysis, thus paving the way for the treatment of osteoporosis using bioactive inorganic materials.