VEGF Expression in Diabetic Rats Promotes Alveolar Bone Resorption by <i>Porphyromonas gingivalis</i> LPS

Abstract

Diabetes mellitus is an important risk factor for periodontitis. Although numerous complications are associated with the disease, all of these are attributed to vascular disorders and are closely related to the potent angiogeneic factor vascular endothelial growth factor (VEGF). However, it remains unknown how diabetes mellitus/hyperglycemia-associated VEGF expression affects alveolar bone resorption in the periodontium. The aim of this study was to determine the level of adverse effect on bone resorption of diabetes mellitus-associated VEGF. Therefore, we induced experimental periodontitis with injections of the endotoxin lipopolysaccharide (LPS) from Porphyromonas gingivalis in diabetic rats, measured the level of bone resorption, and observed VEGF expression and localization of osteoclasts in the periodontium. Eight-week-old male Goto-Kakizaki (GK) rats were in the experimental group, and male Wistar rats were in the control group. Experimental periodontitis was induced by injecting P. gingivalis LPS and inserting ligatures. All rats were euthanized and underwent micro X-ray computed tomography (CT) to acquire bone resorption image, in which the distance between the cement-enamel junction and the alveolar bone crest was measured to determine the amount of bone resorption. Samples were prepared and underwent immunohistochemical staining with an anti-VEGF monoclonal antibody and tartrate-resistant acid phosphatase (TRAP) staining. The amount of bone resorption measured by micro X-ray CT images was significantly greater in the experimental group than in the control group. Immunohistochemical staining showed that VEGF expression levels on the alveolar bone surface and around microvessels in the gingival connective tissue were higher in the experimental group than in the control group. On the alveolar bone surface, localization of TRAP-positive cells and bone resorption lacunae from the same sites were observed in both groups. These results suggest that VEGF expression in the periodontium caused by hyperglycemia in rats with diabetes mellitus affects P. gingivalis LPS-induced alveolar bone resorption.

Effects of C-reactive protein on the expression of matrix metalloproteinases and their inhibitors via Fcγ receptors on 3T3-L1 adipocytes

“…Thus, CRP might facilitate ECM degradation via upregulation of expression of multiple MMPs, whereas CRP-induced TIMP-1 might contribute to proteolysis regulation to maintain the frame of adipose tissue. Nutritional excess is one of the most important risk factors for obesity; association of obesity with systemic or local infection with organisms like Chlamydia pneumoniae or Porphyromonas gingivalis (periodontitis-related pathogen) has been documented 36 - 39 . These findings and our results suggest that elevation of CRP levels caused by these infections may act as a modification factor for exacerbating obesity via facilitation of ECM protein turnover in adipose tissue.…”