{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T16:03:05Z","timestamp":1788624185288,"version":"build-2803163510"},"reference-count":76,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771092"],"award-info":[{"award-number":["81771092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970910"],"award-info":[{"award-number":["81970910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondria\u2010driven macrophage dysregulation contributes significantly to inflammatory disease progression; however, the mechanism underlying bisphosphonate\u2010related osteonecrosis of the jaw (BRONJ) remains unclear. This study demonstrates that zoledronic acid (ZA) disrupts mitochondrial bioenergetic function in macrophages, leading to elevated mitochondrial membrane potential, excessive mitochondrial reactive oxygen species (mtROS), and increased HIF\u20101\u03b1 expression, which together promote a pro\u2010inflammatory transition in macrophages. ZA further inhibits autophagy by activating the TLR4\u2010MyD88\/PI3K\u2010AKT\u2010mTOR pathway, preventing the clearance of dysfunctional mitochondria and sustaining superoxide production. Genetic loss of\n                    <jats:italic>Atg5<\/jats:italic>\n                    in innate immune cells disrupts autophagosome maturation and markedly worsens ZA\u2010induced BRONJ development. To restore mitochondrial degradation and biofunction, ZA\u2010loaded nanoparticles incorporating the mTOR inhibitor rapamycin (ZDPR) are developed. ZDPR effectively prevents BRONJ and exerts therapeutic benefits in osteoporosis and osteolysis. These findings highlight bone\u2010targeted mitochondria rescue as a promising strategy to enhance antiresorptive therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517586","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T03:24:32Z","timestamp":1765164272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti\u2010Resorptive Therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-8732","authenticated-orcid":false,"given":"Hang","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxi","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mumin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Orthopaedic Trauma Institute (OTI) Trauma Center Zhongda Hospital School of Medicine Southeast University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuepeng","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Lab of Digital Medical Engineering Jiangsu Laboratory for Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University  Nanjing 211189 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziji","family":"Ling","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songsong","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyao","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-0381","authenticated-orcid":false,"given":"Hongbing","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing 210029 China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Stomatology Nanjing Medical University  Nanjing 210029 China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1808082"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3657"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.19425"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30072-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116289"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2022.02.008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-024-00969-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4756"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2015.02.02"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159865"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012718"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2017.05.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2014.46"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097948"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0042"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djq516"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115560"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2023.116899"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801791RR"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70"},{"key":"e_1_2_9_21_1","first-page":"59","volume":"11","author":"Hong W. L.","year":"2024","journal-title":"Mil. Med. Res."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2395149"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14893"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130996"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2234228"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3324"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1011"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad4017"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2366-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.07.012"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.064"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh2841"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.01.004"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2128019"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2437908"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.07.015"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513861200"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323376"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76207"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.08.072"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl041"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27609-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-024-02425-9"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10785"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-018-2655-z"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-025-06547-3"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.2009.0049"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03602-z"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.004"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.12.005"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250684"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.005"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-025-01224-x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102061"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102305"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00392-4"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01503-7"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00930-8"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00542-2"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01513-9"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002790"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.05.027"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0162-4"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3535"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2186112"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143576"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz0748"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.12.017"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2024.05.014"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204871"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00676-9"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109653"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090592"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00396-8"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202517586","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202517586","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202517586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:27:27Z","timestamp":1772958447000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202517586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,7]]},"references-count":76,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/advs.202517586"],"URL":"https:\/\/doi.org\/10.1002\/advs.202517586","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,7]]},"assertion":[{"value":"2025-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e17586"}}