Emdogain stimulates matrix degradation by osteoblasts

Emdogain stimulates matrix degradation by osteoblasts
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DOI:
10.1177/154405910808700805
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发表时间:
2008-08-01
影响因子:
7.6
通讯作者:
Domae, N.
Domae, N.
中科院分区:
医学1区
文献类型:
--
作者:
Goda, S.;Inoue, H.;Domae, N.

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Emdogain已在临床上用于牙周再生,但其潜在的分子机制目前尚不清楚。在这项研究中,我们假设Emdogain通过成骨细胞刺激I型胶原的降解。我们发现Emdogain以一种依赖于基质金属蛋白酶的方式促进细胞介导的I型胶原的降解。虽然MG-63细胞自发地产生一种酶原形式的基质金属蛋白酶-1,但恩多卡因处理显著地诱导了这种酶的活性形式的产生。我们证明了MG63细胞以MEK1/2依赖的方式对Emdogain的反应产生了基质金属蛋白酶-3。同时,U0126阻断MEK1/2的激活可显著抑制活性形式的基质金属蛋白酶-1的产生,而不影响胶原酶的总产量。这些结果表明,Emdogain通过激活胶原酶-1来促进组织再生,胶原酶可以降解骨组织微环境中的基质蛋白。
Emdogain has been used clinically for periodontal regeneration, although the underlying molecular mechanisms are not clear at present. In this study, we hypothesized that Emdogain stimulated degradation of type I collagen via osteoblasts. We showed that Emdogain enhanced cell-mediated degradation of type I collagen in an MMP-dependent manner. Although MG-63 cells spontaneously produced a zymogen form of MMP-1, treatment with Emdogain significantly induced the generation of the active form of this enzyme. We demonstrated that MMP-3 was produced from MG63 cells in response to Emdogain in a MEK1/2-dependent manner. Concomitantly, blocking of MEK1/2 activation by U0126 significantly inhibited the generation of the active form of MMP-1 without affecting the total production of this collagenase. These results suggest that Emdogain facilitates tissue regeneration through the activation of the collagenase, MMP-1, that degrades matrix proteins in bone tissue microenvironments.