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However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force\u2013guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell\u2013derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force\u2013activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.<\/jats:p>","DOI":"10.1177\/00220345241262706","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T02:17:52Z","timestamp":1722910672000},"page":"937-947","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics"],"prefix":"10.1177","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-6729","authenticated-orcid":false,"given":"H.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Cranial-Facial Growth and Development Center, Peking University School and Hospital of Stomatology, Haidian District, Beijing, PR China"},{"name":"National Center of Stomatology & National Clinical Research Center for Oral Diseases & National 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