Overexpression of Shox2 leads to congenital dysplasia of the temporomandibular joint in mice.
Overexpression of Shox2 leads to congenital dysplasia of the temporomandibular joint in mice.
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DOI：
10.3390/ijms150813135
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发表时间：
2014-07-24
影响因子：
5.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Li X;Liang W;Ye H;Weng X;Liu F;Liu X
我们先前的研究报道了Shox 2的失活导致颞下颌关节（TMJ）的发育不良和强直，并且用人Shox替换Shox 2部分地挽救了具有过早磨损的关节盘的表型。然而，Shox 2活性在TMJ发育中的机制仍有待阐明。在这项研究中，我们调查了先天性TMJ发育不良的Wnt 1-Cre; pMes-stop Shox 2小鼠的分子和细胞基础。我们发现髁状突和关节窝发育不良主要发生在出生后第二周。Wnt 1-Cre; pMes-stop Shox 2小鼠的发育不良TMJ表现出I型胶原、II型胶原、Ihh和Gli 2的损失。原位酶谱和免疫组织化学进一步证实了基质金属蛋白酶（MMP），MMP 9和MMP 13的上调，伴随着细胞凋亡的显着增加。此外，野生型和突变型小鼠胚胎TMJ中细胞增殖和Sox 9、Runx 2和Ihh的表达没有差异。我们的研究结果表明，Shox 2的过度表达导致细胞外基质的损失和细胞凋亡的增加，在TMJ发育不良，通过上调MMPs和下调Ihh信号通路。
Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway.
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影响因子：
7
作者：
Liu, Y. -D.;Liao, L. -F.;Zhang, H. -Y.;Lu, L.;Jiao, K.;Zhang, M.;Zhang, J.;He, J. -J.;Wu, Y. -P.;Chen, D.;Wang, M. -Q.
通讯作者：
Wang, M. -Q.
影响因子：
3
作者：
Spears, R;Oakes, R;Hutchins, B
通讯作者：
Hutchins, B
影响因子：
7.6
作者：
Ochiai T;Shibukawa Y;Nagayama M;Mundy C;Yasuda T;Okabe T;Shimono K;Kanyama M;Hasegawa H;Maeda Y;Lanske B;Pacifici M;Koyama E
通讯作者：
Koyama E
影响因子：
2.7
作者：
Yu, Ling;Liu, Hongbing;Chen, YiPing
通讯作者：
Chen, YiPing
影响因子：
3.5
作者：
Clement-Jones, M;Schiller, S;Rappold, GA
通讯作者：
Rappold, GA