Effects of overexpression of basic helix-loop-helix transcription factor Dec1 on osteogenic and adipogenic differentiation of mesenchymal stem cells
Effects of overexpression of basic helix-loop-helix transcription factor Dec1 on osteogenic and adipogenic differentiation of mesenchymal stem cells
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DOI：
10.1016/j.ejcb.2005.12.007
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发表时间：
2006-05-01
影响因子：
6.6
通讯作者：
Kato, Yukio
中科院分区：
文献类型：
--
作者：
Iwata, Tomoyuki;Kawamoto, Takeshi;Kato, Yukio
我们最近报道了碱性螺旋-环-螺旋转录因子Dec 1的强制表达加速了颗粒培养物中间充质干细胞（MSC）的软骨形成分化（Shen，M.，吉田，E.，严文，Kawamoto，T.，Suardita，K.，Koyano，Y.，Fujimoto，K.，Noshiro，M.，加藤，Y.，2002.碱性螺旋-环-螺旋蛋白DEC 1在早期和终末阶段促进软骨细胞分化。J. Blol. 277，50112-50120）。由于MSC具有多向分化潜能，我们研究了Dec 1在人骨髓源性MSC成骨和成脂分化中的作用。MSC在含有地塞米松、β-甘油磷酸盐和抗坏血酸的培养基中进行成骨诱导后，Dec 1表达从第5天到第14天逐渐增加，而Dec 1 mRNA的表达水平在成脂诱导后第3天和第7天显著降低。表达Dec 1的腺病毒感染提高了几种骨特征分子的mRNA水平，如骨桥蛋白、PTH受体和碱性磷酸酶，即使在没有成骨诱导培养基的情况下，尽管它对Runx 2表达或钙化几乎没有影响。在成骨诱导培养基中，Dec 1过表达增强骨桥蛋白和碱性磷酸酶的表达，并诱导基质钙化。用siRNA敲低Dec 1抑制诱导的MSC表达成骨细胞表型。使用MSC培养物，我们还证实了Dec 1的强制表达抑制了脂肪形成分化。这些发现表明，Dec 1通过诱导几个，但不是全部，骨相关基因的表达来调节MSC的成骨分化。(c)2006年Elsevier GmbH。All rights reserved.
We recently reported that forced expression of basic helix-loop-helix transcription factor Dec1 accelerated chondrogenic differentiation of mesenchymal stem cells (MSC) in pellet cultures (Shen, M., Yoshida, E., Yan, W., Kawamoto, T., Suardita, K., Koyano, Y., Fujimoto, K., Noshiro, M., Kato, Y., 2002. Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages. J. Blol. Chem. 277, 50112-50120). Since MSC have multilineage differentiation potential, we investigated the roles of Dec1 in osteogenic and adipogenic differentiation of human bone marrow-derived MSC. After osteogenic induction of MSC in medium containing dexamethasone, beta-glycerophosphate, and ascorbic acid, Dec1 expression gradually increased from day 5 to day 14, while expression levels of Dec1 mRNA markedly decreased on days 3 and 7 after adipogenic induction. Infection with adenovirus expressing Dec1 raised mRNA levels of several bone characteristic molecules such as osteopontin, PTH receptor, and alkaline phosphatase, even in the absence of the osteogenic induction medium, although it had little effect on Runx2 expression or calcification. In the osteogenic induction medium, Dec1 overexpression enhanced the expression of osteopontin and alkaline phosphatase and induced matrix calcification. Knockdown of Dec1 with siRNA suppressed the expression of osteoblastic phenotype by the induced MSC. Using MSC cultures, we also confirmed that forced expression of Dec1 suppressed adipogenic differentiation. These findings suggest that Dec1 modulates osteogenic differentiation of MSC by inducing the expression of several, but not all, bone-related genes. (c) 2006 Elsevier GmbH. All rights reserved.