MMP-1 (collagenase-1) and MMP-13 (collagenase-3) differentially regulate markers of osteoblastic differentiation in osteogenic cells.
MMP-1 (collagenase-1) and MMP-13 (collagenase-3) differentially regulate markers of osteoblastic differentiation in osteogenic cells.
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MMP-1（胶原酶-1）和 MMP-13（胶原酶-3）差异调节成骨细胞中成骨细胞分化的标志物。
DOI：
10.1016/j.matbio.2008.07.005
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Kapila S
中科院分区：
文献类型：
--
作者：
Hayami T;Kapila YL;Kapila S
先前的研究已经证明了成骨细胞的成骨细胞表型与胶原酶的组成性或刺激性表达之间存在反比关系。然而，细胞分泌的胶原酶对成骨细胞分化的直接影响，以及关键的胶原溶解性MMP-1和MMP-13对特定成骨细胞标志物调节的精确贡献尚未阐明。在地塞米松存在和不存在的情况下，将早期传代的成骨人牙周膜（PDL）细胞暴露于外源性胶原酶-1。或者，通过用针对MMP-1和/或MMP-13的cDNA或siRNA转染细胞来调节内源性胶原酶。然后测定特异性成骨细胞标记物和胶原酶表达和活性。增加外源性胶原酶或内源性MMP-1和MMP-13的浓度产生剂量依赖性AP活性降低。相反，随着MMP-1或MMP-13 siRNA浓度的增加，观察到AP活性的剂量依赖性增加。MMP-1的过表达导致Runx 2、骨连接蛋白（ON）、骨桥蛋白（OP）、骨唾液酸蛋白（BSP）和骨钙素（OC）的mRNA水平显著降低，而Osterix（Osx）mRNA水平升高。相反，MMP-1的敲低导致Runx2、ON、OP、BSP和OC水平的显著增加和Osx水平的降低。MMP-13过表达导致Osx、OP和BSP水平降低，而其敲低导致Osx和OP水平显著升高，ON水平显著降低。细胞-基质提取物中基质分子（包括胶原I（α 1））的增加导致其各自mRNA的变化。MMP-1和MMP-13的同时抑制导致所有成骨细胞标志物测定的显着增加。MMP-1和-13差异调节成骨细胞标志物，它们的联合抑制对于PDL细胞中成骨细胞表型的阐述是重要的。
Previous studies have demonstrated an inverse relationship between constitutive or stimulated collagenase expression and osteoblastic phenotype of osteogenic cells. However, the direct effects of cell-secreted collagenases on osteoblastic differentiation, and the precise contributions of the key collagenolytic MMPs, MMP-1 and -13 to the modulation of specific osteoblastic markers have not been elucidated. Early passage osteogenic human periodontal ligament (PDL) cells were exposed to exogenous collagenase-1 in the presence and absence of dexamethasone. Alternatively, endogenous collagenases were modulated by transfecting the cells with cDNA or siRNA to MMP-1 and/or -13. Specific osteoblastic markers and collagenase expression and activity were then assayed. Increasing concentrations of exogenous collagenase or endogenous MMP-1 and MMP-13 produced a dose-dependent decrease in AP activity. Conversely, a dose-dependent increase in AP activity was observed with increasing concentrations of MMP-1 or MMP-13 siRNA. Overexpression of MMP-1 resulted in a significant decrease in Runx2, osteonectin (ON), osteopontin (OP), bone sialoprotein (BSP) and osteocalcin (OC), but an increase in osterix (Osx) mRNA levels. In contrast, knockdown of MMP-1 caused a significant increase in Runx2, ON, OP, BSP and OC levels and a decrease in Osx levels. MMP-13 overexpression resulted in diminished levels of Osx, OP and BSP, while its knockdown caused a significant increase in Osx and OP levels and a significant decrease in ON levels. The accretion of matrix molecules including collagen I(α1) in cell-matrix extracts paralleled the changes in their respective mRNAs. Simultaneous suppression of both MMP-1 and MMP-13 resulted in significant increases in all osteoblastic markers assayed. MMP-1 and -13 differentially regulate osteoblastic markers and their combined suppression is important for the elaboration of an osteoblastic phenotype in PDL cells.
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DOI：
10.1083/jcb.200409115
发表时间：
2005-05-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee S;Jilani SM;Nikolova GV;Carpizo D;Iruela-Arispe ML
通讯作者：
Iruela-Arispe ML
影响因子：
2.6
作者：
Basdra, EK;Komposch, G
通讯作者：
Komposch, G
影响因子：
4.2
作者：
Chien, HH;Lin, WL;Cho, MI
通讯作者：
Cho, MI
DOI：
10.1016/j.bbrc.2006.12.234
发表时间：
2007-03-23
影响因子：
3.1
作者：
Kosaki, Naoto;Takaishi, Hironari;D'Armiento, Jeanine
通讯作者：
D'Armiento, Jeanine
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B