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Here, we find that targeted activation of retinoic acid\u2010related orphan receptor \u03b1 (ROR\u03b1) by SR1078 in the early stage of bone defect repair can significantly promote in situ bone regeneration of DM rats. Bone regeneration relies on the activation of macrophage ROR\u03b1 in the early bone repair, but ROR\u03b1 of DM rats fails to upregulation as hyperglycemic inflammatory microenvironment induced IGF1\u2010AMPK signalling deficiency. Mechanistic investigations suggest that ROR\u03b1 is vital for macrophage\u2010induced migration and proliferation of bone mesenchymal stem cells (BMSCs) via a CCL3\/IL\u20106 depending manner. In summary, our study identifies ROR\u03b1 expressed in macrophages during the early stage of bone defect repair is crucial for in situ bone regeneration, and offers a novel strategy for bone regeneration therapy and fracture repair in DM patients.<\/jats:p>","DOI":"10.1111\/cpr.13474","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T07:45:31Z","timestamp":1681371931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Targeting <scp>ROR\u03b1<\/scp> in macrophages to boost diabetic bone regeneration"],"prefix":"10.1111","volume":"56","author":[{"given":"Yufeng","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Stomatology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"School of Stomatology Tongji Medical College, Huazhong University of Science and Technology  Wuhan 430030 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