Authors
Huajian Shan, Chaowen Bai, Yifei Zhu, Chenyang Xu, Sonngtao Li, Qize Sun, Chang She, Jinyu Bai, Cong Cao, Yitian Yang, Xiaozhong Zhou
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e76837. Aug 10, 2026. Epub Aug 10, 2026.
Abstract
BMP2 serves as a pivotal regulator of skeletal development, homeostasis, and repair. Previously, we demonstrated that Gαi1/3 (G protein subunit alpha i1/3) is not only involved in G protein-coupled receptor (GPCR) signal transduction but also acts as a key mediator of tyrosine kinase receptor signaling. However, its role in bone formation and BMP2 signaling remains elusive. In this study, we report that the expression of Gαi1/3 is significantly downregulated in the bone tissue of patients with senile osteoporosis. Gαi1/3 double knockout mice exhibited delayed skeletal development and reduced bone mass. Mechanistically, Gαi1/3 is required for BMP2 signal transduction, as its deletion impaired BMP2 downstream signaling. In BMSCs (bone marrow-derived mesenchymal stem cells), Gαi1/3 knockout suppressed BMP2-induced osteogenesis, while overexpression enhanced it. In the femoral fracture model, knockdown of Gαi1/3 in BMSCs reduced the ability of BMP2 to promote fracture healing. Furthermore, in neonatal mice with conditional knockout of Gαi1/3 in BMSCs, skeletal development was delayed. Gab1 is indispensable for Gαi1/3-mediated BMP2 signaling, as Gαi1/3 binds to both the BMP2 receptor and Gab1 to mediate BMP2 biological function. Collectively, our findings reveal the critical role of the Gαi1/3-Gab1 axis in BMP2 signaling and osteogenesis, providing potential therapeutic targets for osteoporosis and bone repair.
PMID:
42572923
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.
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