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

碱性成纤维细胞生长因子（bFGF）牙周再生治疗的建立

基本信息

批准号：
10557201
负责人：
MURAKAMI Shinya
金额：
$ 7.17万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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.

几种生长因子或细胞因子最近受到关注，因为它们能够积极调节牙周膜（PDL）细胞的各种细胞功能，并且已经评估了局部应用这些因子对牙周组织再生的影响。在这项研究中，我们研究了碱性成纤维细胞生长因子（bFGF）在牙周组织创伤愈合和再生中的作用。在比格犬和灵长类动物中通过手术创建牙槽骨缺损（2壁、3壁和分叉II类骨缺损）。将重组bFGF局部应用于人工骨缺损。应用后6周或8周，对牙周再生进行形态学和组织形态计量学分析。在应用bFGF的所有位点中，观察到显著的牙周膜形成，新牙骨质沉积和新骨形成的量大于对照位点。我们发现值得注意的是，在bFGF位点没有观察到上皮向下生长、强直或牙根吸收的情况。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细胞的碱性磷酸酶活性和矿化结节形成的诱导。有趣的是，我们观察到，层粘连蛋白在PDL细胞，这在血管生成中起着重要的作用，是专门上调bFGF刺激，但I型胶原的mRNA水平下调。本研究表明，bFGF可以作为一种积极诱导牙周组织再生的治疗方式。体外研究结果表明，通过抑制牙周膜细胞向矿化组织形成细胞的分化，bFGF可能通过促进血管生成和诱导未成熟牙周膜细胞的生长，在伤口愈合中发挥重要作用，并可能反过来加速牙周再生。