New Strategy for Periodontal Treatment Based on Control of Angiogenesis in Periodontal Tissues using VEGF and Anti-VEGF.

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Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. To clarify the role of VEGF in periodontal lesion, we investigated 1) the-properties of VEGF expression in the cells derived from human periodontal tissues in culture, 2) the detection of the changing levels of VEGF in gingival crevicular fluid (GCF) following two months of scaling and root planning (SRP), and 3) the effects of VEGF on human periodontal ligament fibroblasts (HPLF) culture through the induction of osteogenic markers and nodule formation. The results showed that 1) human gingival fibroblasts (HGF) constitutively produced VEGF and levels were significantly enhanced by stimulation with Ve and OMP from A.actinomycetemcomitans and P.gingivalis. Supernatant from cultures of Ve-and OMP-stimulated HGF strongly induced vascular permeability enhancement, and 2) that total amounts of VEGF in GCF might indicate the severity of periodontitis and t … More he concentration of VEGF could predict the healing response of periodontal tissues following SRP. These results suggest that VEGF may be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema. Furthermore, the results revealed 3) that VEGF enhanced the expression of c-fos, osteopontin, osteocalcin, bone morphogenesis protein-2 and periodontal ligament associated protein-1 in HPLF culture by stimulation with VEGF^<121> and VEGF^<165>, but not in HGF. VEGF^<165> induced these osteogenic markers more strongly than VEGF^<121>. The alkaline phosphatase activity and calcium concentration were up-regulated after HPLF culture was stimulated with VEGF^<121> and VEGF^<165> for 15 days, while nodule formations also up-regulated after 21 days. These results suggest that HPLF has a phenotype similar to osteoblasts after being stimulated with VEGF, and VEGF may have an important role in initiating the process of periodontal tissue healing. Less