MOLECULAR BASIS OF PERIODONTAL REGENERATION

我们的长远目标是发展全面而有效的 能够获得可重复和可靠的牙周治疗 再生。为此，基础和临床相结合的方法 提出了本文的研究方向。具体目标是：1)确定是否 牙周膜表皮生长因子受体 成纤维细胞与维持未分化状态有关 以及EGF-R的丧失在多大程度上与它们的 分化，2)研究其表达和表达的调节 维甲酸和转化生长因子合成EGF-R (转化生长因子)-α]，并了解维甲酸 对PDL成纤维细胞EGF-R的调节作用，3)体内效应评价 血小板衍生生长因子-BB(PDGF-BB)，PDGF-AA的组合， PDGF-BB、EGF和/或维甲酸对牙周组织再生的影响 III在Beagle犬身上产生的分叉损伤。也是为了评估 PDGF-BB和胰岛素样生长因子-I的联合作用 成骨蛋白-1(OP-1)等骨形态发生蛋白 Beagle犬模型，以及4)利用生长评估治疗效果 因子调控再生与引导组织法相结合 在比格犬身上使用屏障膜。 在基础研究中，我们建议了解EGF-R在PDL中的作用 成纤维细胞在维持PDL细胞未分化状态中的作用 调节它们向成骨细胞的分化，并可能 体外培养成牙骨质细胞。此外，其基本机制是 维甲酸对EGF-R基因的调节作用将被研究。为了这些 目的、原位配基结合分析等技术 杂交、免疫沉淀、免疫金标记、Northern 印迹、转染、寡核苷酸缺失分析和凝胶 将进行迟缓试验。这些研究将帮助我们 了解维持PDL细胞表型的基本机制 调节它们向成骨细胞的分化，并可能 成牙骨质细胞。这些信息也可能有助于更好地理解 骨细胞分化的结果。 还将努力将基础研究与临床联系起来。 应用大鼠再植和Beagle犬模型。快速 PDL的修复将通过有选择地重新填充PDL来实现 引导组织再生联合生长因子诱导成纤维细胞 调制方法。有能力维持的因素(S) PDL细胞的未分化状态将在临床上应用 调控细胞有序增殖和迁移，防止PDL细胞 早期分化为成骨细胞，从而导致关节强直 PDL的愈合。这样的知识对秩序将是有价值的 牙齿支持组织的再生。 这些研究将促进对白纹伊蚊生物学知识的进步 牙周组织的修复和再生。 此外，这种全面的牙周再生疗法将 为达致“健康口腔健康”的推广目标作出贡献 2000人“关于减少牙周病引起的牙齿缺失。

Our long-term objective is to develop a comprehensive and effective therapy capable of achieving reproducible and reliable periodontal regeneration. In doing so, combined approaches of basic and clinical research are proposed. The specific aims are: 1) To determine if the epidermal growth factor-receptor (EGF-R) of periodontal ligament (PDL) fibroblasts is associated with maintaining the undifferentiated state of these cells, and to what extent the loss of EGF-R is related to their differentiation, 2) To investigate the regulation of expression and synthesis of EGF-R by retinoic acid and EGF [transforming growth factor (TGF)-alpha], and to understand the mechanism by which retinoic acid regulates EGF-R on PDL fibroblasts, 3) To evaluate the in vivo effects of platelet-derived growth factor-BB (PDGF-BB), a combination of PDGF-AA, PDGF-BB, EGF, and/or retinoic acid on periodontal regeneration of class- III furcation lesions created in the beagle dog. Also to evaluate the effects of a combination of PDGF-BB and insulin-like growth factor-I, and bone morphogenic proteins such as osteogenic protein-1 (OP-1) in the beagle dog model, and 4) To assess the efficacy of therapy using growth factor-modulated regeneration combined with the guided tissue method using barrier membranes in the beagle dog. In basic research, we propose to understand the role of the EGF-R on PDL fibroblasts in maintaining the undifferentiated state of PDL cells and regulating their differentiation into osteoblasts and possibly cementoblasts in vitro. Furthermore, the fundamental mechanism by which retinoic acid regulates the EGF-R gene will be investigated. For these purposes, techniques such as the ligand binding assay, in situ hybridization, immunoprecipitation, immunogold labeling, Northern blotting, transfection, oligonucleotide deletion analyses and gel retardation assay will be applied. These studies will help us to understand the basic mechanisms maintaining the phenotype of PDL cells and regulating their differentiation into osteoblasts and possible cementoblasts. This information may also lead to better understanding of bone cell differentiation. An effort will also be made to link the basic research to clinical application using the rat reimplantation and beagle dog models. Rapid repair of the PDL will be achieved by selective repopulation of PDL fibroblasts using guided tissue regeneration combined with growth factor- modulated method. The factor(s) capable of maintaining the undifferentiated state of PDL cells will be clinically applied to regulate orderly cell proliferation and migration, and prevent PDL cell premature differentiation into osteoblasts and thus, ankylosis during healing of the PDL. Such knowledge will be valuable for orderly regeneration of the tooth supporting tissues. These studies will promote advances in knowledge of the biology of the periodontium, and repair and regeneration of the periodontal tissues. Furthermore, this comprehensive periodontal regenerative therapy will contribute to achieving the oral health promotion objective of "Healthy People 2000" regarding reducing tooth loss due to periodontal disease.