{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:42:05Z","timestamp":1791895325778,"version":"4.3.4"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81771092"],"award-info":[{"award-number":["81771092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,22]]},"abstract":"<jats:p>\n                    Bisphosphonate-related (BP-related) osteonecrosis of the jaw (BRONJ) is one of the severe side effects of administration of BPs, such as zoledronic acid (ZA), which can disrupt the patient\u2019s quality of life. Although the direct target of skeletal vasculature and bone resorption activity by BPs has been phenomenally observed, the underlying mechanism in BRONJ remains largely elusive. Thus, it is urgently necessary to discover effective therapeutic targets based on the multifaceted underlying mechanisms in the development of BRONJ. Here, we determined the inhibitory role of ZA-treated macrophages on osteoclast differentiation and type H vessel formation during tooth extraction socket (TES) healing. Mechanistically, ZA activated the NF-\u03baB signaling pathway and then induced p65 nuclear translocation in macrophages to promote miR-149-5p transcription, resulting in impaired osteoclast differentiation via directly binding to the\n                    <jats:italic>Traf6<\/jats:italic>\n                    3\u2032-UTR region. Moreover, we identified that miR-149-5p\u2013loaded extracellular vesicles derived from ZA-treated bone marrow\u2013derived macrophages could regulate biological functions of endothelial cells via the Rap1a\/Rap1b\/VEGFR2 pathway. Furthermore, local administration of chemically modified antagomiR-149-5p was proven to be therapeutically effective in BRONJ mice. In conclusion, our findings illuminate the dual effects of miR-149-5p on skeletal angiogenesis and bone remolding, suggesting it as a promising preventive and therapeutic target for BRONJ.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.159865","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T14:00:46Z","timestamp":1661090446000},"source":"Crossref","is-referenced-by-count":32,"title":["Macrophage miR-149-5p induction is a key driver and therapeutic target for BRONJ"],"prefix":"10.1172","volume":"7","author":[{"given":"Xin","family":"Shen","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases and"},{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China."},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 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