Establishment of periodontal regenerative therapy by basic libroblast growth lactor (bFGF)

近年来，一些生长因子或细胞因子因其能够积极调节牙周韧带（PDL）细胞的各种细胞功能而受到关注，并对局部应用这些因子对牙周组织再生的影响进行了评估。在这项研究中，我们研究了碱性成纤维细胞生长因子（bFGF）在牙周组织伤口愈合和再生中的作用。牙槽骨缺损（2-壁、3-壁和分叉II级骨缺损）是在比格犬和灵长类动物中手术产生的。重组bFGF用于人工骨缺损的局部修复。应用后6周和8周，对牙周再生进行形态学和组织形态学分析。在所有应用bFGF的部位，观察到明显的牙周韧带形成，新牙骨质沉积和新骨形成的数量大于对照组。我们发现值得注意的是，在bFGF部位没有观察到上皮向下生长、强直或根吸收的情况。体外研究表明，bFGF增强人PDL细胞的增殖反应，表达FGF受体1和2，但抑制PDL细胞诱导碱性磷酸酶活性和矿化结节形成。有趣的是，我们观察到在血管生成中起重要作用的PDL细胞中，层粘胶蛋白的mRNA水平在bFGF刺激下特异性上调，而I型胶原的mRNA水平则下调。本研究表明bFGF可作为积极诱导牙周组织再生的治疗手段之一。体外研究结果表明，bFGF可能通过抑制PDL细胞向矿化组织形成细胞的分化，促进血管生成和诱导未成熟PDL细胞的生长，从而在伤口愈合中发挥重要作用，从而加速牙周再生。

Several growth factors or cytokines have recently received attention because of their ability to actively regulate various cellular functions of periodontal ligament (PDL) cells and the effects of topical application of such factor (s) on periodontal tissue regeneration has been evaluated. In this study, we examined the role of basic fibroblast growth factor (bFGF) in the wound healing and regeneration of periodontal tissues. Alveolar bone defects (2-wall, 3-wall and furcation class II bone defects) were surgically created in beagle dogs and primates. Recombinant bFGF was topically applied to the artificial bony defects. Six or eight weeks after application, the periodontal regeneration was morphologically and histomorphometrically analyzed. In all sites where bFGF was applied, significant periodontal ligament formation with new cementum deposits and new bone formation was observed in amounts greater than in the control sites. We found it noteworthy that no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF sites. In vitro studies demonstrated that bFGF enhances the proliferative responses of human PDL cells, which express FGF receptor-1 and-2, but inhibits the induction of alkaline phosphatase activity and mineralized nodule formation by PDL cells. Interestingly, we observed that the mRNA level of laminin in PDL cells, which plays an important role in angiogenesis, was specifically upregulated by bFGF stimulation, but that of type I collagen was down regulated. The present study demonstrates that bFGF can be applied as one of the therapeutic modalities which actively induce periodontal tissue regeneration. The results of in vitro studies suggest that by suppressing the cytodifferentiation of PDL cells into mineralized tissue forming cells, bFGF may play important roles in wound healing by promoting angiogenesis and inducing the growth of immature PDL cells, and may in turn accelerate periodontal regeneration.