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Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte\u2013preosteoblast axis regulated by FGF9\u2013FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.<\/jats:p>","DOI":"10.1002\/advs.202506954","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T11:36:56Z","timestamp":1757158616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FGF9\u2013FGFR2 Signaling via Osteocytes\u2010Preosteoblasts Crosstalks to Mediate Mechanotransduction\u2010Driven Intramembranous Osteogenesis in the Underdeveloped Maxilla"],"prefix":"10.1002","volume":"12","author":[{"given":"Yiwen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthodontics Nanjing Stomatological Hospital Affiliated Hospital of Medical School Institute of Stomatology Nanjing University  30 Zhongyang Road Nanjing Jiangsu 210008 China"},{"name":"Department of Stomatology the First People's Hospital of Changzhou the Third Affiliated 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