Growth Differentiation Factor 5 (GDF-5) Induces Matrix Metalloproteinase 2 (MMP-2) Expression in Periodontal Ligament Cells and Modulates MMP-2 and MMP-13 Activity in Osteoblasts:

Growth Differentiation Factor 5 (GDF-5) Induces Matrix Metalloproteinase 2 (MMP-2) Expression in Periodontal Ligament Cells and Modulates MMP-2 and MMP-13 Activity in Osteoblasts:
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生长分化因子 5 (GDF-5) 诱导牙周膜细胞中基质金属蛋白酶 2 (MMP-2) 表达并调节成骨细胞中 MMP-2 和 MMP-13 活性:

DOI:
10.4137/btri.s8120
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发表时间:
2010
影响因子:
3.8
通讯作者:
Y. Sawa
Y. Sawa
中科院分区:
医学3区
文献类型:
--
作者:
Y. Hatakeyama;J. Hatakeyama;Y. Maruya;K. Oka;E. Tsuruga;T. Inai;Y. Sawa

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生长分化因子5 (Growth differentiation factor 5, GDF-5)是转化生长因子β (TGF-)超家族中的一员,在牙周组织中表达,促进牙周韧带(PDL)细胞的细胞外基质(extracellular matrix, ECM)形成。基质金属蛋白酶(MMP)是降解ECM的蛋白水解酶,在PDL细胞中表达。迄今为止,人们对PDL细胞中MMP合成和分泌的调控知之甚少。本研究的目的是研究GDF-5对PDL细胞中MMP产生和活性的影响。培养3天后,GDF-5增加了小鼠PDL组织细胞中I型胶原α 2 (Col I2)和MMP-2基因的表达。由于PDL细胞是异质群体,我们在成骨细胞系中检测了明胶溶解活性和基因表达谱。在培养6、12、24和48小时后,GDF-5增加了成骨细胞中Col I2和MMP基因的表达。培养7天后明胶酶谱分析显示,GDF-5还能促进MMP-2的活性。另一方面,当p38 MAP激酶抑制剂SB202190存在时,MMP-2活性被阻断。综上所述,GDF-5可能同时增加PDL细胞中I型胶原和成骨样细胞中MMP-2的基因表达,成骨细胞中p38 MAP激酶通路可能参与了GDF-5诱导的MMP-2酶活性的调控。
Growth differentiation factor 5 (GDF-5), a member of the transforming growth factor beta (TGF-) superfamily expressed in periodontal tissues, promotes extracellular matrix (ECM) in periodontal ligament (PDL) cells. Matrix metalloproteinases (MMP) are proteolytic enzymes that degrade ECM and are expressed in PDL cells. To date, little is known about the regulation of MMP synthesis and secretion in PDL cells. The aim of this study is to examine the effects of GDF-5 on MMP production and activity in PDL cells. GDF-5 increased both collagen type I alpha 2 (Col I2) and MMP-2 gene expression in cells derived from mouse PDL tissues after 3 days of culture. Because PDL cells represent a heterogeneous population, we examined gelatinolytic activity and gene expression profiles in an osteoblast cell line. After 6, 12, 24, and 48 hours of culture, GDF-5 increased both Col I2 and MMP gene expression in osteoblasts. GDF-5 also promoted MMP-2 activity as revealed by gelatin zymography after 7 days of culture. In the presence of the p38 MAP kinase inhibitor SB202190, on the other hand, MMP-2 activity was blocked. Taken together, these results indicate that GDF-5 may increase simultaneously the gene expression of type I collagen and MMP-2 in the osteoblast-like cells among the PDL cells and p38 MAP kinase pathway in osteoblast could involve in the regulation of MMP-2 enzyme activity induced by GDF-5.
DOI: 10.1210/endo.139.3.5818
发表时间: 1998-03
期刊: Endocrinology
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