ZM-306416 prevents ovariectomy-induced bone loss by promoting osteoblastogenesis and inhibiting osteoclastogenesis - bone marrow-derived macrophages

Micro-CT scan and immunostaining were used to determine bone phenotypes in vivo. Drug library screening demonstrated that ZM enhances ALP activity in osteoblasts, indicating its potential as a pro-osteogenic agent. ZM exerts dual effects by promoting osteoblast differentiation through the Wnt/β-catenin signaling pathway and simultaneously inhibiting osteoclast differentiation by the NF-κB and MAPK signaling pathways.

In an OVX mouse model, ZM effectively prevents bone loss by stimulating osteoblast formation and inhibiting osteoclast development. Our study revealed that ZM has a dual anti-osteoporosis effect by promoting osteoblastogenesis and inhibiting osteoclastogenesis, mediated via activation of Wnt/β-catenin signaling and suppression of NF-κB/MAPK cascades. These findings suggest that ZM could be a promising therapeutic strategy for alleviating osteoporosis.