biostudies-literatureJiang XNational Natural Science Foundation of China (National Science Foundation of China)18https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920663biostudies-literatureUnknown18(1)Alveolar bone resorption during the socket healing process compromises subsequent restoration outcomes. Recent clinical evidence suggests that dental implant placement can effectively prevent such bone loss, yet the mechanisms remain elusive. In this study, combined multi-dataset screening pinpointed sorting nexin 5 (Snx5) as a potential regulator of mechanotransduction, whose expression was downregulated in early peri-implant bone remodeling zones following implant placement. Functional studies showed that loss of Snx5 abolished the additional osteogenic enhancement normally induced by mechanical stimulation. In vivo, Snx5 deficiency disrupted the mechanosensitive activation of LepR⁺ MSCs and compromised implant-induced osteogenesis. Mechanistically, Snx5 facilitates the recyclInternational journal of oral scienceImplantation awakens peri-implant osteogenic potential via Snx5-EGFR axis-mediated mechanical transduction.PMC129206638220103382350001Huang JJiang XFeng YWeng YWang HWang ZfalseImplantation awakens peri-implant osteogenic potential via Snx5-EGFR axis-mediated mechanical transduction.Alveolar bone resorption during the socket healing process compromises subsequent restoration outcomes. Recent clinical evidence suggests that dental implant placement can effectively prevent such bone loss, yet the mechanisms remain elusive. In this study, combined multi-dataset screening pinpointed sorting nexin 5 (Snx5) as a potential regulator of mechanotransduction, whose expression was downregulated in early peri-implant bone remodeling zones following implant placement. Functional studies showed that loss of Snx5 abolished the additional osteogenic enhancement normally induced by mechanical stimulation. In vivo, Snx5 deficiency disrupted the mechanosensitive activation of LepR⁺ MSCs and compromised implant-induced osteogenesis. Mechanistically, Snx5 facilitates the recycl2026-01-01T00:00:00Z2026 Feb2026-07-16T13:02:03.195Z2026-07-09T10:56:33.853ZS-EPMC129206634171461610.1038/s41368-025-00423-2