BPAG1 promotes osteoclastogenesis and postmenopausal osteoporosis via activating ERK signaling pathway.

Osteoclasts (OCs), as the primary cells responsible for bone resorption, play a crucial role in the development of osteoporosis. Yet, how OC differentiation is regulated and involved in the occurrence of OP remains unknown. Here, we notice that BPAG1 is closely related to OC differentiation and osteoporosis. The upregulation of BPAG1 promotes OC differentiation in vitro, whereas its downregulation inhibits this process. Research on the mechanism indicates that BPAG1 can induce OC differentiation via regulating the phosphorylation of ERK. Notably, inhibiting ERK impaired the increase in OC differentiation caused by BPAG1 overexpression. In addition, inhibiting BPAG1 reversed bone destruction in osteoporotic mice. Hence, our research revealed the mechanism by which BPAG1 regulates OC differentiation and bone resorption by activating ERK. Targeting BPAG1 is a potential strategy for treating osteoporosis.