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Here, we identify bone lymphatics as an essential component of the regenerative microenvironment in the mandible and long bones. We demonstrate that bone lymphatic endothelial cells (LECs) constitute a specialized endothelial population that is transcriptionally and spatially distinct from periosteal LECs. During skeletal repair, bone LECs reactivate a regenerative transcriptional programme, and promote mandibular and fracture healing. In osteonecrosis of the jaw and periodontitis, bone lymphatic-associated signalling is disrupted, identifying impaired lymphatic function as a shared feature of mandibular disease. Therapeutic activation of VEGFC\u2013FLT4 signalling during injury or mandibular disease restores lymphangiogenesis, enhances osteogenesis, and markedly improves bone regeneration. Together, our findings advance the paradigm-shifting role of bone lymphatics positive regulators of bone regeneration and identify lymphatic activation as a promising therapeutic strategy to enhance bone regeneration in mandibular diseases.<\/jats:p>","DOI":"10.64898\/2026.08.06.743157","type":"posted-content","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:20:18Z","timestamp":1786029618000},"source":"Crossref","is-referenced-by-count":0,"title":["Bone Lymphatic Endothelial Cells Form a Distinct Skeletal Population and Drive Skeletal Repair"],"prefix":"10.64898","author":[{"given":"Sanyam","family":"Jain","sequence":"first","affiliation":[{"name":"Tissue and Tumor Microenvironments Lab, Cancer Discovery and Regenerative Medicine Program, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Tissue and Tumor Microenvironments Lab, Cancer Discovery and Regenerative Medicine Program, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"},{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghan","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makarand V","family":"Risbud","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Graduate Program in Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-5782","authenticated-orcid":false,"given":"Junyu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1911-5495","authenticated-orcid":false,"given":"Anjali P.","family":"Kusumbe","sequence":"additional","affiliation":[{"name":"Tissue and Tumor Microenvironments Lab, Cancer Discovery and Regenerative Medicine Program, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"},{"name":"Multidisciplinary Institute of Ageing (MIA-Portugal), University of Coimbra, Coimbra 3004-504, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080904450550000_2026.08.06.743157v1.1","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1002\/jbmr.4171","article-title":"Bone vasculature and bone marrow vascular niches in health and disease","volume":"35","year":"2020","journal-title":"Journal of Bone and Mineral Research"},{"key":"2026080904450550000_2026.08.06.743157v1.2","doi-asserted-by":"crossref","unstructured":"Roy, N. et al. 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