{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:19:10Z","timestamp":1785421150177,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Natural Science Foundation","award":["L2510105"],"award-info":[{"award-number":["L2510105"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82401142"],"award-info":[{"award-number":["82401142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82405493"],"award-info":[{"award-number":["82405493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82401142"],"award-info":[{"award-number":["82401142"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82405493"],"award-info":[{"award-number":["82405493"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Beijing High-Level Innovation and Entrepreneurship Talent Support Program Young Backbone Talent Projects","award":["G202532301"],"award-info":[{"award-number":["G202532301"]}]},{"name":"Beijing Stomatological Hospital, Capital Medical University","award":["YSP202311"],"award-info":[{"award-number":["YSP202311"]}]},{"name":"Beijing Stomatological Hospital, Capital Medical University","award":["CXJJ25109"],"award-info":[{"award-number":["CXJJ25109"]}]},{"award":["YSP202311"],"award-info":[{"award-number":["YSP202311"]}],"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CXJJ25109"],"award-info":[{"award-number":["CXJJ25109"]}],"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Oral Diseases","award":["SKLOD2024OF14"],"award-info":[{"award-number":["SKLOD2024OF14"]}]},{"award":["SKLOD2024OF14"],"award-info":[{"award-number":["SKLOD2024OF14"]}],"id":[{"id":"https:\/\/ror.org\/00pvqk557","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Aging is a major risk factor for impaired bone-defect healing, and dysregulation of the immune microenvironment, especially macrophage dysfunction, is closely linked to this process. Interleukin-34 (IL-34) plays a crucial role in macrophage biology; however, its role in aging-related bone-defect healing remains elusive. Herein, young and aged male C57BL\/6 mice were utilized to establish a tibial bone defect model. Microcomputed tomography, histological staining, flow cytometry, RNA sequencing and in vitro cell experiments were conducted to explore the role and mechanism of action of IL-34 in aging-impaired bone healing. Aging markedly decreased bone mass, inhibited osteogenic differentiation and impaired bone defect healing in mice. Moreover, aging reduces macrophage numbers at bone defects and suppresses M2 polarization, with the drop likely driven by recruitment, survival or proliferation defects rather than impaired recruitment exclusively. IL-34 was a key differentially expressed gene that was downregulated in aged mice, which was further confirmed at the protein level. Furthermore, aging decreased IL-34 secretion by macrophages and impaired macrophage proliferation and M2 polarisation. Thus, aging impairs tibial bone-defect healing by downregulating IL-34 expression, decreasing macrophage infiltration, and inhibiting M2 polarisation. Furthermore, IL-34 acts as a pro-reparative cytokine that promotes bone healing by regulating macrophage function, suggesting its role as a potential therapeutic target for enhancing age-related bone repair.<\/jats:p>","DOI":"10.3390\/ijms27156683","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-34 Regulates Macrophage Polarization and Bone Defect Healing in Aged Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0672-0565","authenticated-orcid":false,"given":"Wen","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zanxu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, School of Stomatology, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaochen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1210\/endrev\/bnac008","article-title":"Fracture Healing in the Setting of Endocrine Diseases, Aging, and Cellular Senescence","volume":"43","author":"Saul","year":"2022","journal-title":"Endocr. 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