Matsuda N, Lin W L, Kumar N M, Cho M I, Genco R J
Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo.
J Periodontol. 1992 Jun;63(6):515-25. doi: 10.1902/jop.1992.63.6.515.
The mitogenic, chemotactic, and synthetic responses of rat periodontal ligament (PDL) fibroblastic cells to epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), recombinant human platelet-derived growth factor (rhPDGF)-AB, rhPDGF-BB, natural (n) PDGF-AB, and insulin-like growth factor-I (IGF-I) were examined in vitro using PDL cells obtained from the coagulum of healing tooth sockets. PDGFs and IGF-I have potent and comparable mitogenic effects on PDL fibroblastic cells. The maximum mitogenic effect of PDGFs was observed at the concentration of 10 ng/ml, whereas that of IGF-I was seen at concentrations higher than 100 ng/ml. In contrast, EGF induced moderate, and TGF-beta inhibitory mitogenic responses. The combination of rhPDGF-AB with either EGF or TGF-beta demonstrated comparable mitogenic potency, equivalent to the level of PDGF alone regardless of the mitogenic effect of other growth factors. The combination of rhPDGF-AB and IGF-I, however, showed a synergistic effect revealing the highest mitogenic effect among all individual growth factors as well as any combinations of the growth factors tested. Similarly, PDL fibroblastic cells demonstrated strong chemotactic responses to both IGF-I and PDGFs. The maximum effect was observed by IGF-I at concentrations higher than 10 ng/ml, followed by rhPDGF-BB at 0.1 ng/ml, rhPDGF-AB and nPDGF at concentrations ranging from 0.1 to 1 ng/ml. TGF-beta revealed no, and EGF slightly increased, chemotactic effects. IGF-I slightly enhanced the synthesis of total protein, whereas other factors had no significant effect. However, both rhPDGF-AB and TGF-beta stimulated collagen synthesis. On the other hand, IGF-I showed no effect on collagen synthesis, while EGF suppressed collagen synthesis. These findings suggest that rhPDGF-BB and IGF-I stimulate proliferation and chemotaxis of PDL fibroblastic cells. In addition, the combination of these growth factors further increases the mitogenic effect. rhPDGF-AB also stimulates collagen synthesis by PDL fibroblastic cells. Thus, rhPDGF-BB and IGF-I may have important roles in promotion of PDL healing, and consequently, may be useful for clinical application in periodontal regenerative procedures.
利用从愈合牙槽血凝块中获取的牙周膜（PDL）细胞，在体外检测了大鼠牙周膜成纤维细胞对表皮生长因子（EGF）、转化生长因子-β（TGF-β）、重组人血小板衍生生长因子（rhPDGF）-AB、rhPDGF-BB、天然（n）PDGF-AB和胰岛素样生长因子-I（IGF-I）的促有丝分裂、趋化和合成反应。血小板衍生生长因子（PDGFs）和胰岛素样生长因子-I（IGF-I）对牙周膜成纤维细胞具有强大且相当的促有丝分裂作用。PDGFs在10 ng/ml浓度时观察到最大促有丝分裂作用，而IGF-I在高于100 ng/ml的浓度时出现最大促有丝分裂作用。相比之下，EGF诱导中等程度的促有丝分裂反应，而TGF-β则产生抑制性促有丝分裂反应。rhPDGF-AB与EGF或TGF-β联合使用时，显示出相当的促有丝分裂效力，无论其他生长因子的促有丝分裂作用如何，其效力与单独使用PDGF时相当。然而，rhPDGF-AB与IGF-I联合使用时，显示出协同效应，在所有单独的生长因子以及所测试的生长因子组合中，其促有丝分裂作用最强。同样，牙周膜成纤维细胞对IGF-I和PDGFs均表现出强烈的趋化反应。IGF-I在高于10 ng/ml的浓度时观察到最大效应，其次是0.1 ng/ml的rhPDGF-BB，rhPDGF-AB和nPDGF在0.1至1 ng/ml的浓度范围内。TGF-β未显示趋化作用，而EGF略微增加了趋化作用。IGF-I略微增强了总蛋白的合成，而其他因子没有显著影响。然而，rhPDGF-AB和TGF-β均刺激了胶原蛋白的合成。另一方面，IGF-I对胶原蛋白合成没有影响，而EGF抑制了胶原蛋白的合成。这些发现表明，rhPDGF-BB和IGF-I刺激牙周膜成纤维细胞的增殖和趋化作用。此外，这些生长因子的组合进一步增强了促有丝分裂作用。rhPDGF-AB也刺激牙周膜成纤维细胞的胶原蛋白合成。因此rhPDGF-BB和IGF-I在促进牙周膜愈合中可能具有重要作用，因此可能对牙周再生程序的临床应用有用。
