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The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+<\/jats:sup>\/podoplanin (PDPN)+<\/jats:sup> lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)\u2010associated periodontitis and ligature\u2010induced periodontitis. Further, PDPN+<\/jats:sup>\/alpha\u2010smooth muscle actin (\u03b1SMA)\u2212<\/jats:sup> lymphatic capillaries are increased, whereas PDPN+<\/jats:sup>\/\u03b1SMA+<\/jats:sup> collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP\u2010positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno\u2010associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+<\/jats:sup>\/\u03b1SMA+<\/jats:sup> collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+<\/jats:sup>\/\u03b1SMA\u2212<\/jats:sup> lymphatic capillaries are increased, whereas LYVE1+<\/jats:sup>\/\u03b1SMA+<\/jats:sup> collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation\u2010mediated alveolar bone loss. \u00a9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5456","type":"journal-article","created":{"date-parts":[[2020,5,17]],"date-time":"2020-05-17T12:03:50Z","timestamp":1589717030000},"page":"323-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effect of VEGFC<\/scp> on lymph flow and inflammation\u2010induced alveolar bone loss"],"prefix":"10.1002","volume":"251","author":[{"given":"Hua","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases Nanjing Medical University Nanjing PR China"},{"name":"Department of Basic Science of Stomatology Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases Nanjing Medical University Nanjing PR 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