Divergent upstream osteogenic events contribute to the differential modulation of MG63 cell osteoblast differentiation by MMP-1 (collagenase-1) and MMP-13 (collagenase-3).
Divergent upstream osteogenic events contribute to the differential modulation of MG63 cell osteoblast differentiation by MMP-1 (collagenase-1) and MMP-13 (collagenase-3).
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DOI：
10.1016/j.matbio.2011.04.003
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发表时间：
2011-05
期刊：
影响因子：
6.9
通讯作者：
Kapila, Sunil
中科院分区：
文献类型：
--
作者：
Hayami, Takayuki;Kapila, Yvonne L.;Kapila, Sunil
先前我们发现MMP-1（胶原酶-1）和MMP-13（胶原酶-3）在异质人群的人牙周韧带细胞中对成骨细胞标志物的表达有差异调节。这些差异反应的机制尚不清楚，但可能是由于早期成骨转录因子调控的差异。本研究的目的是阐明在成骨细胞特异性转录因子和标记物的层次中，MMP-1和-13介导的成骨细胞分化调节的差异出现在哪里。我们发现MMP-1过表达导致BMP-2、Dlx5、AP、OP、BSP显著降低，TGF-β1、MSX2显著升高。而MMP-13过表达导致Runx2、OP、BSP显著降低，TGF-β1、MSX2、OC显著升高。MMP-1的下调导致所有成骨细胞标志物显著增加。MMP-13基因下调仅在TGF-β1、MSX2和Osx中显著升高，在Runx2和OC中显著降低。两种MMPs的共同抑制导致除Runx2外的所有成骨细胞标志物显著增加。与MMP-13相比，MMP-1在调节成骨细胞转录因子和标记物方面具有更强大和更广泛的作用。最后，在所检测的标记物和转录因子中，Runx2是MMP-1抑制诱导的最早期转录因子，而Osx和MSX2是MMP-13调控的最早期转录因子。这些数据表明，MMP-1和-13对MG63细胞成骨标记物的差异调节可能是由于它们对参与成骨细胞分化的不同信号通路的调节。
Previously we showed that MMP-1 (collagenase-1) and MMP-13 (collagenase-3) differentially regulate the expression of osteoblastic markers in a heterogenous population of primary human periodontal ligament cells. The mechanisms for these differential responses are not known, but may result from divergence in regulation of early osteogenic transcription factors. The purpose of this study was to elucidate where in the hierarchy of osteoblast-specific transcription factors and markers the differences in MMP-1- and -13-mediated regulation of osteoblastic differentiation arise. We found that the overexpression of MMP-1 resulted in significant decreases in BMP-2, Dlx5, AP, OP and BSP and increases in TGF-β1 and MSX2. In contrast, MMP-13 overexpression resulted in significant decreases in Runx2, OP and BSP, and increases in TGF-β1, MSX2 and OC. The knockdown of MMP-1 caused significant increases in all osteoblastic markers. MMP-13 knockdown produced significant increases only in TGF-β1, MSX2 and Osx, but decreases in Runx2 and OC. Suppression of both MMPs together resulted in significant increases of all osteoblastic markers except Runx2. MMP-1 had a more robust and generalized effect in regulating osteoblast transcription factors and markers than MMP-13. Finally, of the markers and transcription factors assayed, Runx2 is the most early stage transcription factor induced by suppression of MMP-1, while Osx and MSX2 are the most early stage transcription factors regulated by MMP-13. These data show that MMP-1’s and -13’s differential regulation of osteoblastic markers in MG63 cells likely results from their modulation of divergent signaling pathways involved in osteoblastic differentiation.
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影响因子：
4.3
作者：
Almazin, Salah M.;Dziak, Rosemary;Ciancio, Sebastian G.
通讯作者：
Ciancio, Sebastian G.
影响因子：
4.2
作者：
Chien, HH;Lin, WL;Cho, MI
通讯作者：
Cho, MI
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
发表时间：
2008-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Hayami T;Kapila YL;Kapila S
通讯作者：
Kapila S
影响因子：
4.8
作者：
D'Alonzo, RC;Kowalski, AJ;Partridge, NC
通讯作者：
Partridge, NC
影响因子：
6.2
作者：
Jikko, A;Harris, SE;Damsky, CH
通讯作者：
Damsky, CH