{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:40:48Z","timestamp":1776145248383,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020207","name":"Health Commission of Sichuan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020207","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate the mechanism of medication\u2010related osteonecrosis of the jaw (MRONJ), which is challenging to prevent and treat, to facilitate the development of precise prevention and treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Osteoclast\u2010derived exosomes were extracted and their roles in cell migration, osteogenesis, angiogenesis, and the mechanism of MRONJ were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Osteoclast\u2010derived exosomes were taken up by human umbilical vein endothelial cells and osteoblasts. Cell migration and vascularization decreased in cells treated with zoledronic acid (ZA)\u2010induced exosomes. VEGFR2 mRNA and protein expression decreased, while Caspase9 mRNA and protein expression increased. The migration and osteogenic differentiation of osteoblasts induced by exosomes from ZA\u2010treated osteoclasts decreased, and the mRNA and protein expression of Notch1\u2010Hes1\/Hey increased. In\u00a0vivo, ZA\u2010treated osteoclast\u2010derived exosomes caused decreased trabecular volume, number, and thickness and increased trabecular separation in the extraction sockets. Alkaline phosphatase and tartrate\u2010resistant acid phosphatase activities decreased, and the number of H\u2010type vessels decreased in the ZA\u2010treated group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ZA may contribute to MRONJ by affecting the exocytotic components produced by osteoclasts through the VEGFR2\u2010Caspase9 and Notch1\u2010Hes1\/Hey signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70080","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:17:29Z","timestamp":1762143449000},"page":"492-503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteoclast\u2010Derived Exosomes Promote\n                    <scp>MRONJ<\/scp>\n                    via the\n                    <scp>VEGFR2<\/scp>\n                    \u2010Caspase9 and Notch1\u2010Hes1\/Hey Signaling Pathways"],"prefix":"10.1111","volume":"32","author":[{"given":"Kun","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Oral and Maxillofacial Surgery West China Hospital of Stomatology, Sichuan University  Chengdu Sichuan China"},{"name":"Department of Stomatology The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Oral and Maxillofacial Surgery West China Hospital of Stomatology, Sichuan University  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