Schip1 promotes osteoclast differentiation via Taok1-mediated activation of the p38 MAPK signaling pathway in mouse models of osteoporosis

Schip1 serves as a pivotal regulatory factor in both the Hippo pathway and the PDGFB signaling pathway, which are significant in the pathogenesis of osteoporosis. However, the role of Schip1 in osteoporosis remains to be elucidated. In this study, we demonstrated for the first time that Schip1 acted as a positive regulator in osteoclastogenesis. We observed a significant upregulation of Schip1 expression during Rankl-induced osteoclast differentiation, and the suppression of Schip1 expression notably reduced Rankl-induced osteoclast formation. Functionally, Schip1 interacted with Taok1 to activate the p38 MAPK signaling pathway, which promoted osteoclast differentiation. Genetic ablation of Schip1 in mice resulted in pronounced osteosclerosis compared to wild-type controls. Furthermore, mice with deletion of Schip1 exhibited significantly mitigated osteoporosis following ovariectomy. Collectively, our findings establish Schip1 as a regulator of osteoclast differentiation and suggest its potential as a therapeutic target for osteoporosis.