Characteristic Growth Factor Actions Involved in Periodontal Regeneration

牙周治疗的目的是再生因牙周炎而破坏的牙周结缔组织，恢复附着在牙根表面的结缔组织。这需要牙周膜组织、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，新的牙骨质形成是必不可少的步骤，因为没有新的牙骨质就不可能获得附着。因此，我们研究了牙骨质中的生长因子，它可以刺激牙周膜细胞的增殖，调节其向成牙骨质细胞的分化。目前，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，发现牙骨质衍生生长因子对肝素有中等的亲和力，在表皮生长因子或血清因子的存在下，它对成纤维细胞的促有丝分裂活性被协同增强。在第一次研究中，我们证明了牙骨质衍生生长因子是一种类似胰岛素的…由于分子大小不同、内部氨基酸序列不同、对成骨细胞的促有丝分裂反应以及N-糖基硅化等原因，类生长因子-I分子较多，但不完全相同。其次，通过检测细胞周期蛋白E和细胞周期蛋白E依赖的激酶活性，探讨了细胞周期蛋白E和表皮生长因子在人成纤维细胞中协同促有丝分裂作用的机制。通过将人IGF-Ia基因导入小鼠成骨细胞克隆牙周膜细胞，建立了新的能结构性表达大量人IGF-I的小鼠克隆细胞系。该细胞系对碱性成纤维细胞生长因子(BFGF)和碱性磷酸酶(ALPase)活性的反应性高于对照细胞系。有趣的是，内源性IGF-I的这些作用不能通过加入适量的重组人IGF-I来完全补偿。综合这些结果，CGF是一种类似IGF-I的分子，成骨细胞或成牙骨质细胞产生的内源性IGF-I在牙周创伤愈合再生过程中可能比外源性成熟IGF-I发挥更大的作用。较少

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