Role of MSX1 in Osteogenic Differentiation of Human Dental Pulp Stem Cells.
Role of MSX1 in Osteogenic Differentiation of Human Dental Pulp Stem Cells.
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DOI：
10.1155/2016/8035759
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发表时间：
2016
影响因子：
4.3
通讯作者：
Kato Y
中科院分区：
文献类型：
--
作者：
Goto N;Fujimoto K;Fujii S;Ida-Yonemochi H;Ohshima H;Kawamoto T;Noshiro M;Shukunami C;Kozai K;Kato Y
MSH Homeobox 1(Msx1)编码一种转录因子，与四肢和包括骨骼和牙齿在内的颅面组织的胚胎发育有关。虽然Msx1调节幼年动物颅骨中的成骨细胞分化，但对人类细胞成骨潜能的影响却知之甚少。在本研究中，我们研究了Msx1在人乳牙牙髓干细胞成骨分化中的作用。当这些细胞暴露在成骨诱导培养液中时，在第4-12天，矮小相关转录因子-2(RUNX2)、骨形态发生蛋白-2(BMP2)、碱性磷酸酶(ALPL)和骨钙素(OCN)的mRNA水平以及碱性磷酸酶(OCN)的活性增加，随后在第14天基质被钙化。然而，Msx1被小干扰RNA敲除后，成骨细胞相关基因的表达、碱性磷酸酶活性和钙化的诱导被取消。有趣的是，DNA微阵列和聚合酶链式反应分析显示，Msx1基因敲除可诱导胆固醇合成途径中的固醇调节元件结合蛋白2(SREBP2)转录因子及其下游靶基因。抑制胆固醇合成可促进各种间充质细胞向成骨细胞分化。因此，Msx1可能下调胆固醇合成相关基因，以确保人牙髓干细胞向成骨细胞分化。
Msh homeobox 1 (MSX1) encodes a transcription factor implicated in embryonic development of limbs and craniofacial tissues including bone and teeth. Although MSX1 regulates osteoblast differentiation in the cranial bone of young animal, little is known about the contribution of MSX1 to the osteogenic potential of human cells. In the present study, we investigate the role of MSX1 in osteogenic differentiation of human dental pulp stem cells isolated from deciduous teeth. When these cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL), and osteocalcin (OCN) mRNA levels, as well as alkaline phosphatase activity, increased on days 4–12, and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity, and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells.
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影响因子：
4.2
作者：
Okamoto, Yosuke;Sonoyama, Wataru;Kuboki, Takuo
通讯作者：
Kuboki, Takuo
影响因子：
14
作者：
Lee, Yeonju;Schmid, Marian J.;Reinhardt, Richard A.
通讯作者：
Reinhardt, Richard A.
影响因子：
1.9
作者：
Feng, Xiao-yu;Zhao, Yu-ming;Ge, Li-hong
通讯作者：
Ge, Li-hong
影响因子：
2.5
作者：
Orestes-Cardoso, SM;Nefussi, JR;Berdal, A
通讯作者：
Berdal, A
影响因子：
7.7
作者：
Cheng SL;Behrmann A;Shao JS;Ramachandran B;Krchma K;Bello Arredondo Y;Kovacs A;Mead M;Maxson R;Towler DA
通讯作者：
Towler DA