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Previously, we demonstrated that G\u03b1i1\/3 (G protein subunit alpha i1\/3) is not only involved in G protein\u2010coupled 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 G\u03b1i1\/3 is significantly downregulated in the bone tissue of patients with senile osteoporosis. G\u03b1i1\/3 double knockout mice exhibited delayed skeletal development and reduced bone mass. Mechanistically, G\u03b1i1\/3 is required for BMP2 signal transduction, as its deletion impaired BMP2 downstream signaling. In BMSCs (bone marrow\u2013derived mesenchymal stem cells), G\u03b1i1\/3 knockout suppressed BMP2\u2010induced osteogenesis, while overexpression enhanced it. In the femoral fracture model, knockdown of G\u03b1i1\/3 in BMSCs reduced the ability of BMP2 to promote fracture healing. Furthermore, in neonatal mice with conditional knockout of G\u03b1i1\/3 in BMSCs, skeletal development was delayed. Gab1 is indispensable for G\u03b1i1\/3\u2010mediated BMP2 signaling, as G\u03b1i1\/3 binds to both the BMP2 receptor and Gab1 to mediate BMP2 biological function. Collectively, our findings reveal the critical role of the G\u03b1i1\/3\u2010Gab1 axis in BMP2 signaling and osteogenesis, providing potential therapeutic targets for osteoporosis and bone repair.<\/jats:p>","DOI":"10.1002\/advs.76837","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:29:52Z","timestamp":1786354192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["G\u03b1i1\/3 Are Essential for BMP2\u2010Induced Osteogenesis by Bridging BMP Receptors to the Gab1 Signaling Complex"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6903-7178","authenticated-orcid":false,"given":"Huajian","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu China"},{"name":"Clinical Research Center of Neurological Disease Institution of Neuroscience Second 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