{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T17:27:13Z","timestamp":1786814833769,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"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":["82102602"],"award-info":[{"award-number":["82102602"]}],"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":["82272176"],"award-info":[{"award-number":["82272176"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Impaired fracture healing remains a major clinical challenge, with approximately 10% of fractures progressing to nonunion or delayed union. Although numerous studies have focused on strategies to promote fracture healing, the mechanisms governing the initiation phase of repair remain poorly understood. This study aimed to investigate the contribution of macrophage\u2010derived TGF\u2010\u03b21 to the initiation of early fracture repair. A murine femoral osteotomy model was used to study fracture healing. We examined the temporal relationship among bone healing, callus maturation, pSmad2\/3 positive cells, and osteoprogenitors. TGF\u2010\u03b21 signaling was systemically inhibited using a neutralizing antibody. Macrophages were selectively depleted in LysM\u2010iDTR mice by diphtheria toxin administration. The source and expression levels of TGF\u2010\u03b21 at the fracture site were determined by pSmad2\/3 staining and RT\u2010qPCR. Fracture healing was assessed using micro\u2010CT, histomorphometry, and immunohistochemistry. TGF\u2010\u03b21 signaling peaked during the inflammatory phase and preceded osteoprogenitor recruitment. Systemic inhibition of TGF\u2010\u03b21 or selective macrophage depletion before fracture establishment severely disrupted mesenchymal stem cell (MSC) recruitment and bone formation. In contrast, late\u2010stage macrophage depletion did not substantially affect bone healing. CD86+ macrophages were identified as a key early source of TGF\u2010\u03b21. Importantly, local delivery of TGF\u2010\u03b21 via hydrogel microspheres during the early stage rescued osteogenic repair in macrophage\u2010deficient mice. CD86+ macrophage\u2010derived TGF\u2010\u03b21 is essential for initiating fracture repair by recruiting MSCs and promoting osteogenesis. Targeting this pathway may represent a novel therapeutic strategy to enhance bone regeneration in cases of impaired healing.<\/jats:p>","DOI":"10.1096\/fj.202600696rr","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T17:25:32Z","timestamp":1785000332000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage Derived\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 Recruits\n                    <scp>BMSCs<\/scp>\n                    for Initiation of Bone Formation During Fracture Healing"],"prefix":"10.1096","volume":"40","author":[{"given":"Kaihang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Shanghai Tenth People's Hospital Tongji University School of Medicine  Shanghai People's Republic of 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