{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:29:58Z","timestamp":1789414198772,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A15012155"],"award-info":[{"award-number":["2021A15012155"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bisphosphonate\u2010related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long\u2010term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma delta (\u03b3\u03b4) T cells predominantly distribute in mucosal tissues and play an important role in both immune modulation and bone metabolism; however, the mechanism of \u03b3\u03b4 T cells in the pathogenesis of BRONJ has not been elucidated. Here, we induced BRONJ\u2010like lesions in wild\u2010type (WT) and T\u2010cell receptor delta\u2010deficient (TCR\u03b4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice via intraperitoneal zoledronate injection. Our findings revealed that \u03b3\u03b4 T cells infiltrating BRONJ lesions suppressed osteoblast differentiation, whereas \u03b3\u03b4 T cell depletion in TCR\u03b4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice restored osteogenic function and significantly reduced BRONJ lesion incidence. Mechanistically, we identified matrix metalloproteinase 3 (MMP3) secreted by activated \u03b3\u03b4 T cells as a critical enzyme cleaving membrane\u2010bound Sema4D (mSema4D) into soluble Sema4D (sSema4D). This cleavage product bound to Plexin\u2010B1\/2 receptors on osteoblasts, activating the mTOR signalling pathway to inhibit osteogenic differentiation (ALP\/Runx2 downregulation). To promote the repair of BRONJ lesions, we engineered a dual\u2010functional composite hydrogel (Gel\u2010BG@ab) combining PLGA\u2010PEG\u2010PLGA with mesoporous bioactive glass (BG) and anti\u2010Sema4D antibodies. This composite hydrogel achieved sustained antibody release, effectively neutralising sSema4D, restoring osteoblast activity and reducing the formation of BRONJ\u2010like lesions in\u00a0vivo\n                    <jats:italic>.<\/jats:italic>\n                    This study provides evidence of MMP3\u2010Sema4D\u2010Plexin\u2010B1\/2\/mTOR crosstalk in BRONJ and introduces a targeted biomaterial strategy to disrupt pathogenic feedback loops. The Gel\u2010BG@ab is the integration of immunomodulation and regenerative medicine, providing both theoretical and technical insights for the immune\u2010material combination therapy of BRONJ.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70114","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T05:22:06Z","timestamp":1757049726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Soluble\n                    <scp>Sema4D<\/scp>\n                    From \u03b3\u03b4 T Cells Exerts Osteoblast Inhibition via Plexin\u2010B\/\n                    <scp>mTOR<\/scp>\n                    Signalling Contributing to Pathogenesis of Bisphosphonate\u2010Related Osteonecrosis of the Jaws"],"prefix":"10.1111","volume":"59","author":[{"given":"Lingling","family":"Ou","sequence":"first","affiliation":[{"name":"School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction Guangzhou Medical University  Guangzhou China"},{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Qiao","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoyi","family":"Liao","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiner","family":"Tan","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou 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