期刊
JOURNAL OF PATHOLOGY
卷 251, 期 3, 页码 323-335出版社
WILEY
DOI: 10.1002/path.5456
关键词
alveolar bone loss; lymphatic drainage; periodontitis; TNF-Tg mice; VEGFC
资金
- National Natural Science Foundation of China [81670965, 81970961]
- Natural Science Foundation of Jiangsu Province in China [BK20180034, BK20191346]
- National Key Research and Development Program of China [2018YFA0800804]
- National Institutes of Health PHS awards, USA [R01AG059775]
- Jiangsu Innovation and Entrepreneurship Training Program for College Students [201910312003Z]
The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)(+)/podoplanin (PDPN)(+) 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)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+/alpha-smooth muscle actin (alpha SMA)(-) lymphatic capillaries are increased, whereas PDPN+/alpha SMA(+) collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+/alpha SMA(+) collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1(+)/alpha SMA(-) lymphatic capillaries are increased, whereas LYVE1(+)/alpha SMA(+) 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-mediated alveolar bone loss. (c) 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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