Zeldich E, Koren R, Nemcovsky C, Weinreb M
Department of Oral Biology, Tel-Aviv University, Israel.
J Dent Res. 2007 Jan;86(1):41-6. doi: 10.1177/154405910708600106.
Emdogain, a formulation of Enamel Matrix Proteins, is used clinically for periodontal regeneration to stimulate PDL (periodontal ligament), cementum, and bone formation. Its effects on gingival fibroblasts and tissue have not been thoroughly studied. Therefore, we investigated the mechanisms by which Emdogain affects the cell cycle of human gingival fibroblasts. Without serum, Emdogain (50 microg/mL) induced human gingival fibroblast entry into the S phase and DNA synthesis, but not completion of the cell cycle. With low serum concentrations (0.2-0.5%), Emdogain synergistically induced completion of the cell cycle, resulting in increased cell numbers. The mitogenic response to Emdogain depended on Extracellular Regulated Kinase (ERK) activation, which occurred in two waves, peaking after 15 min and 4 to 6 hrs, since it was abolished by U0126, a specific MAPK inhibitor. Inhibition of the second wave was sufficient to abrogate mitogenesis. This study characterized the mitogenic effect of Emdogain on primary human gingival fibroblasts, its cooperation with serum growth factors, and the key mediatory role of the ERK cascade.
釉基质蛋白制剂Emdogain在临床上用于牙周组织再生，以刺激牙周膜（PDL）、牙骨质和骨的形成。其对牙龈成纤维细胞和组织的影响尚未得到充分研究。因此，我们研究了Emdogain影响人牙龈成纤维细胞细胞周期的机制。在无血清条件下，Emdogain（50微克/毫升）诱导人牙龈成纤维细胞进入S期并进行DNA合成，但不能完成细胞周期。在低血清浓度（0.2 - 0.5%）下，Emdogain协同诱导细胞周期的完成，导致细胞数量增加。Emdogain的促有丝分裂反应依赖于细胞外调节激酶（ERK）的激活，这种激活以两个波峰的形式出现，分别在15分钟和4至6小时后达到峰值，因为它被特异性MAPK抑制剂U0126所阻断。抑制第二波激活足以消除有丝分裂。本研究描述了Emdogain对原代人牙龈成纤维细胞的促有丝分裂作用、其与血清生长因子的协同作用以及ERK级联反应的关键介导作用。
