Characteristic Growth Factor Actions Involved in Periodontal Regeneration

生长因子参与牙周再生的特征性作用

• 批准号: 09671950
• 负责人: MURAKAMI Shinya
• 金额: $ 1.79万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671950/
• 关键词: Periodontitis; Periodontal Regeneration; Cementum; Growth Factor; CGF; Heparin Binding IGF-I like Molecule; IGF-I; Periodontal Ligament Cell; IGF-I前駆体; 不死化細胞株

The aim of reriodontal therapy is to regenerate periodontal connective tissues destroyed by periodontitis and restore connective tissue attachment to root surfaces.This requires regeneration of periodontal ligament tissue, alveolar bone and cementum, and integration of new periodontal ligament tissue into bone and cementum.During the course of periodontal regeneration, new cementum formation is essential step because no attchment gain can be accomplished without new cementum.Therefore, we have studied growth factors in cementum which may stimulate the proliferation of periodontal ligament cells and regulate the differentiation into cementblasts.So far, we purified Cementum-derived Growth Factor(CGF) as a major growth factor in cementum and reported CGF has moderate affinity to heparin and its mitogenic activity to fibroblasts is potentiated synergistically in the presence of Epidermal Growth Factor(EGF) or serum factors.This time in the first study, we showed that CGF is an Insulin lik … More e Growth Factor-I (IGF-I) like molecule but not identical because of some reasons such as different molecular sizes, internal amino acid sequences, mitogenic response to osteoblastic cells, and N-glycosilation.Secondary, we investigated the mechanisms of the synergistic mitogenic effects of CGF and EGF in human fibroblasts by mesuring Cyclin E and Cyclin E dependent kinase activity triggered by both CGF and EGF.The data suggested that high and sustained level of Cyclin E dependent kinase activty may be one important signaling event for the mitogenic synergism induced by both CGF and EGF.Finally, we studied the effects of endogenous IGF-I produced by clonal osteoblastic periodontal ligament cells.We established new mouse clonal cell line which constitutively expresses considerable level of human IGF-I by transfecting human IGF-Ia gene into mouse clonal osteoblastic periodontal ligament cells.This cell line revealed the higher responsiveness to basic Fibroblast Growth Factor (bFGF) and alkaline phosphatase (ALPase) activities than those of the control cell line.Interestingly, these effects by endogenous IGF-I could not be compensated totally by the addition of adequate amount of human recombinant IGF-I.Taken together these results In this report, CGF which is an IGF-I like molecule, and endogenous IGF-I produced by osteoblastic or cementoblastic periodontal ligament cells may play more useful role than exogenous mature IGF-I during the course of periodontal wound healing and regeneration. Less

牙周再生治疗的目的是使被牙周炎破坏的牙周结缔组织再生，并恢复结缔组织对牙根表面的附着。这需要牙周韧带组织、牙槽骨和牙骨质的再生，以及新的牙周韧带组织与骨和牙骨质的整合。在牙周再生过程中，新牙骨质的形成是必不可少的步骤，因为没有新牙骨质就不能获得附着力。因此，我们已经研究了牙骨质中的生长因子，它们可以刺激牙周膜细胞的增殖并调节其向成牙骨质细胞的分化。我们纯化了牙骨质中的主要生长因子--牙骨质衍生生长因子（CGF），并报道了CGF与肝素具有中等亲和力，在表皮生长因子（EGF）或血清因子存在下，CGF对成纤维细胞的促有丝分裂活性协同增强。 ...更多信息 e生长因子-I（IGF-I）样分子，但由于一些原因而不相同，例如不同的分子大小、内部氨基酸序列、对成骨细胞的促有丝分裂反应和N-糖基化。我们通过测定CGF和EGF共同触发的Cyclin E和Cyclin E依赖性激酶活性，研究了CGF和EGF协同促人成纤维细胞有丝分裂作用的机制。细胞周期蛋白E依赖性激酶活性的持续水平可能是CGF和EGF诱导的促有丝分裂协同作用的一个重要信号事件。本研究通过体外培养人牙周膜成骨细胞克隆，建立了一种组成型表达人IGF-Ⅰ的小鼠牙周膜成骨细胞克隆，并对其内源性IGF-Ⅰ的表达进行了研究。Ia基因转染小鼠成骨细胞牙周膜细胞，该细胞系对碱性成纤维细胞生长因子（bFGF）和碱性磷酸酶（ALP）活性的反应性高于对照细胞系。内源性IGF-I的这些作用不能通过加入足够量的人重组IGF-I来完全补偿。综合这些结果在本报告中，作为IGF-I样分子的CGF，成骨细胞或成牙骨质细胞产生的内源性IGF-1可能比外源性成熟IGF-1发挥更大的作用。在牙周创伤愈合和再生过程中。少