1485-P: The Involvement of ANGPTL4 in Periodontitis and the Influence of High Glucose

Periodontitis is a chronic inflammatory disease in which periodontal tissue is destroyed by bacterial infection. Periodontal disease is considered a comorbidity of diabetes due to its high prevalence and severity. However, the molecular mechanisms how diabetes aggravates periodontitis are still unclear. In this study, we investigated the involvement of Angiopoietin-like proteins (ANGPTLs) in periodontitis and the impacts of high glucose. Experimental periodontitis was induced in 6-week-old male Sprague-Dawley rats by placing a nylon suture around the neck of the maxillary second molar. Induction of periodontitis significantly increased the expression of ANGPTL4 in the gingiva. To clarify the involvement of ANGPTL4 in periodontitis, the human gingival fibroblasts (hGFs) were stimulated with LPS of Porphyromonas gingivalis (Pg-LPS), the bacterium most frequently isolated from inflamed sites of adult periodontitis. Pg-LPS significantly increased the gene and protein expression of ANGPTL4 in hGFs but not the gene expression of other ANGPTLs or ANGPTL receptors. Recombinant human ANGPTL4 significantly increased matrix metalloproteinase 13 (MMP13) gene expression in hGFs. We also confirmed that MMP13 expression was increased in the gingiva during experimental periodontitis. Pg-LPS induced MMP13 gene expression in hGFs. Next, we investigated the impacts of high glucose in Pg-LPS-stimulated hGFs. The expression of ANGPTL4 by Pg-LPS was significantly increased in high glucose condition compared with that in normal glucose condition. These results suggest the pivotal role of ANGPTL4 in periodontitis, especially under the high glucose condition.