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

血管内皮生长因子(VEGF)作为一种有效的血管通透性和血管生成的诱导剂，近年来引起了人们的关注。为了阐明血管内皮生长因子在牙周病变中的作用，我们研究了1)体外培养的人牙周组织来源的细胞中血管内皮生长因子的表达特性，2)洁治和根面平整两个月后牙周沟液中血管内皮生长因子水平的变化，以及3)血管内皮生长因子对人牙周膜成纤维细胞(HPLF)培养的影响。结果表明：1)伴生放线菌和牙龈假单胞菌的VE和OMP刺激人牙龈成纤维细胞(HGF)合成血管内皮生长因子(VEGF)，并能显著提高HGF的分泌水平。VE和omp刺激的肝细胞生长因子培养上清液强烈诱导血管通透性增加；2)牙周液中血管内皮生长因子的总量可能反映牙周炎和…的严重程度。更高浓度的血管内皮生长因子可以预测SRP后牙周组织的愈合反应。这些结果提示，血管内皮生长因子可能与牙周炎早期的病因有关，可能与牙周病原体刺激的新生血管形成有关，引起牙周肿胀和水肿。此外，实验结果还表明：(3)在HPLF培养过程中，血管内皮细胞生长因子可促进c-fos、骨桥蛋白、骨钙素、骨形态发生蛋白-2和牙周膜相关蛋白-1的表达，但对HGF无明显影响。血管内皮生长因子对这些成骨标志物的诱导作用强于血管内皮生长因子121。HPLF细胞经血管内皮生长因子121和165刺激15d后，碱性磷酸酶活性和钙离子浓度均升高，21d后结节形成也明显增加。提示HPLF经血管内皮生长因子刺激后具有与成骨细胞相似的表型，在启动牙周组织愈合过程中可能起重要作用。较少

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