Effect of VEGFC on lymph flow and inflammation‐induced alveolar bone loss

Abstract

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 (αSMA)− lymphatic capillaries are increased, whereas PDPN+/αSMA+ 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+/αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+/αSMA− lymphatic capillaries are increased, whereas LYVE1+/αSMA+ 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. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis

“…These changes are consistent with the EC reactions in rheumatoid arthritis, suggesting ECs as active participants and regulators of the inflammatory process 61 , 104 , 105 . We previously demonstrated the functions of lymphatic ECs in the pathogenesis of periodontal inflammation 106 . The current study reveals the function of venous ECs in the recruitment of T cells via the production of proinflammatory cytokines and chemokines (Figure 5 and Figure S6 ).…”

NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation

“…After dehydration, the maxillae were embedded in paraffin for paraffin sections or embedded in Tissue‐Tek OCT compound for frozen sections. The paraffin sections were stained with haematoxylin and eosin (H&E), histochemically for tartrate‐resistant acid phosphatase (TRAP) or alkaline phosphatase (ALP) and analysed as described previously 18 . The frozen sections of Lysm‐Cre/Rosa nTnG mice were mounted with Mounting Medium containing DAPI (Vector) and images were captured with a Leica DM4000 fluorescence microscope, as we reported previously 19 …”

“…For flow cytometric analysis, cells were harvested from periodontal tissues around maxillary second molar as described previously. 18 Single cell suspensions were stained with fluorochrome-conjugated antibodies against CD45. 2…”

RelA/MicroRNA-30a/NLRP3 signal axis is involved in rheumatoid arthritis via regulating NLRP3 inflammasome in macrophages

“…NLRP3-deficient (NLRP3 KO ) mice generated in a C57BL/6J background were kindly provided by Professor Shuo Yang [21]. TNF TG mice (line 3647) were originally obtained from Dr. G. Kollias (Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, Vari, Greece) and have been crossed with C57BL/6J mice for more than 10 generations [22]. NLRP3 +/− female mice and TNF TG male mice were crossed to generate NLRP3 +/− ; TNF TG double-mutant mice, and NLRP3 +/− ; TNF TG males and NLRP3 +/− females were crossed to generate NLRP3 KO /TNF TG mice.…”