MOLECULAR BASIS OF PERIODONTAL REGENERATION

牙周再生的分子基础

• 批准号: 6104697
• 负责人: MOON IL CHO
• 金额: $ 16.97万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104697
• 关键词: cell differentiation; cell growth regulation; dental disorder chemotherapy; disease /disorder model; dogs; epidermal growth factor; fibroblasts; gene expression; growth factor receptors; immunoprecipitation; in situ hybridization; laboratory rabbit; laboratory rat; nonhuman therapy evaluation; northern blottings; osteoblasts; osteocalcin; osteogenesis; periodontium; platelet derived growth factor; receptor expression; retinoate; tissue /cell culture; transforming growth factors; wound healing

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.

我们的长远目标，是制订一套全面而有效的 能够实现可重复和可靠的牙周治疗 再生 在此过程中，基础和临床相结合的方法 研究提出。 具体目标是：1）确定 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， 这些细胞，以及EGF-R的损失在多大程度上与它们的 2）研究其表达调控， 由维甲酸和EGF [转化生长因子]合成EGF-R （TGF）-α]，并了解视黄酸 调节PDL成纤维细胞上的EGF-R，3）评估体内作用 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 在比格犬中产生的III型分叉病变。 此外，为了评估 PDGF-BB和胰岛素样生长因子-I的组合的作用，和 骨形态发生蛋白如成骨蛋白-1（OP-1）， 比格犬模型，以及4）使用生长评估治疗的功效 因子调控再生结合引导组织法 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， 成纤维细胞维持PDL细胞的未分化状态， 调节它们分化成成骨细胞， 体外培养成牙骨质细胞。 此外， 将研究视黄酸调节EGF-R基因。 为这些 目的，技术，如配体结合试验，原位 杂交，免疫沉淀，免疫金标记，北方 印迹、转染、寡核苷酸缺失分析和凝胶电泳 将应用阻滞试验。 这些研究将帮助我们 了解PDL细胞表型维持的基本机制 并调节它们分化成成骨细胞， 成牙骨质细胞。 这些信息也可能导致更好的理解 骨细胞的分化。 还将努力将基础研究与临床联系起来 使用大鼠再植和比格犬模型的应用。 快速 PDL的修复将通过PDL的选择性再增殖来实现 使用引导组织再生结合生长因子的成纤维细胞， 调制法 能够维持 PDL细胞的未分化状态将在临床上应用于 调节细胞有序增殖和迁移，防止PDL细胞 过早分化成成骨细胞，因此， PDL的愈合。 这样的知识对有序的人来说是有价值的。 牙齿支持组织的再生。 这些研究将促进对生物学知识的进步， 牙周组织，牙周组织的修复和再生。 此外，这种全面的牙周再生治疗将 有助达致促进口腔健康的“健康 人2000”关于减少牙齿脱落由于牙周病。