2. Academic Validation
  3. Schip1 promotes osteoclast differentiation via Taok1-mediated activation of the p38 MAPK signaling pathway in mouse models of osteoporosis

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

  • Bone. 2025 Nov:200:117579. doi: 10.1016/j.bone.2025.117579.
Furui Liu 1,  Muhang Tian 2,  Sen Wang 2,  Lei Guo 3,  Fangjing Chen 4
Affiliations

Affiliations

  • 1 Shanghai Tenth People's Hospital Clinical Medical College, Nanjing Medical University, Shanghai, China; Department of Orthopedic, People's Hospital of Wenshan City, Wenshan City, Yunnan Province, China. Electronic address: liufurui@stu.njmu.edu.cn.
  • 2 Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
  • 3 Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: gl11660@rjh.com.cn.
  • 4 Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: fangjingchenzl@163.com.
PMID: 40633827 DOI: 10.1016/j.bone.2025.117579
Abstract

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.

Keywords

Osteoclast; Schip1; Taok1; p38 MAPK.

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