Characteristic Growth Factor Actions Involved in Periodontal Regeneration

牙周治疗的目的是使被牙周炎破坏的牙周结缔组织再生，并使结缔组织附着于牙根表面。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无法获得附着。因此，我们研究了牙骨质中可能刺激牙周膜细胞增殖并调控其向成骨水泥细胞分化的生长因子。到目前为止，我们纯化了骨质衍生生长因子（CGF）作为骨质中的主要生长因子，并报道CGF与肝素具有中等亲和力，其对成纤维细胞的有丝分裂活性在表皮生长因子（EGF）或血清因子的存在下协同增强。这一次，在第一项研究中，我们发现CGF是一种类似胰岛素的生长因子- 1 （igf - 1）的分子，但由于分子大小、内部氨基酸序列、对成骨细胞的有丝分裂反应和n -糖基化等原因而不相同。其次，我们通过测量CGF和EGF触发的Cyclin E和Cyclin E依赖性激酶活性，研究了CGF和EGF在人成纤维细胞中协同有丝分裂作用的机制。这些数据表明，高水平和持续水平的Cyclin E依赖性激酶活性可能是CGF和EGF诱导的有丝分裂协同作用的一个重要信号事件。最后，我们研究了克隆成骨牙周韧带细胞产生的内源性igf - 1的影响。我们通过将人IGF-Ia基因转染到小鼠成骨牙周韧带克隆细胞中，建立了能组成性表达大量人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的这些作用不能完全通过添加足量的人重组IGF-I来弥补。综上所述，CGF是一种类似IGF-I的分子，而由成骨细胞或成胶细胞牙周韧带细胞产生的内源性IGF-I在牙周伤口愈合和再生过程中可能比外源性成熟的IGF-I发挥更大的作用。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