Activation of RXR and RAR signaling promotes myogenic differentiation of myoblastic C2C12 cells

被引：88

作者：

Zhu, Gao-Hui ^{[1
,2
,3
]}

Huang, Jiayi ^{[1
,2
,3
]}

Bi, Yang ^{[1
,2
,3
]}

Su, Yuxi ^{[1
,2
,3
]}

Tang, Yi ^{[4
]}

He, Bai-Cheng ^{[1
,2
,3
]}

He, Yun ^{[1
,2
,3
]}

Luo, Jinyong ^{[1
,2
,3
]}

Wang, Yi ^{[1
,2
,3
]}

Chen, Liang ^{[1
,2
,3
]}

Zuo, Guo-Wei ^{[1
,2
,3
]}

Jiang, Wei ^{[1
]}

Luo, Qing ^{[1
,2
,3
]}

Shen, Jikun ^{[1
]}

Liu, Bo ^{[1
,2
,3
]}

Zhang, Wen-Li ^{[2
,3
,5
]}

Shi, Qiong ^{[1
,2
,3
]}

Zhang, Bing-Qiang ^{[1
,2
,3
]}

Kang, Quan ^{[1
,2
,3
]}

Zhu, Jing ^{[2
,3
]}

Tian, Jie ^{[2
,3
]}

Luu, Hue H. ^{[1
]}

Haydon, Rex C. ^{[1
]}

Chen, Yuan ^{[2
,3
]}

He, Tong-Chuan ^{[1
,2
,3
]}

机构：

[1] Univ Chicago, Med Ctr, Dept Surg, Mol Oncol Lab, Chicago, IL 60637 USA

[2] Chinese Minist Educ, Key Lab Diagnost Med, Chongqing, Peoples R China

[3] Chongqing Med Univ, Affiliated Hosp, Chongqing, Peoples R China

[4] Northwestern Univ, Childrens Mem Hosp, Dept Pathol, Chicago, IL 60614 USA

[5] Sichuan Univ, Huaxi Hosp, Dept Orthopaed Surg, Chengdu 610064, Sichuan, Peoples R China

来源：

DIFFERENTIATION | 2009年 / 78卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Myogenic progenitor cells; Myogenic differentiation; Retinoid signaling; Myoblast cells; Nuclear receptors; BONE MORPHOGENETIC PROTEINS; MESENCHYMAL STEM-CELLS; MUSCLE PROGENITOR CELLS; TRANS-RETINOIC ACID; SKELETAL-MUSCLE; OSTEOBLAST DIFFERENTIATION; OSTEOGENIC DIFFERENTIATION; NUCLEAR RECEPTORS; RECOMBINANT ADENOVIRUSES; DIMETHYL-SULFOXIDE;

D O I：

10.1016/j.diff.2009.06.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Differentiation of embryonic and adult myogenic progenitors under goes a complex series of cell rearrangements and specification events which are controlled by distinct gene regulatory networks. Delineation of the molecular mechanisms that regulate skeletal muscle specification and formation should be important for understanding congenital myopathies and muscular degenerative diseases. Retinoic acid (RA) signaling plays an important role in development. However, the role of RA signaling in adult myogenic progenitors is poorly understood. Here, we investigate the role of RA signaling in regulating myogenic differentiation of myoblastic progenitor cells. Using the mouse myoblast progenitor C2C12 line as a model, we have found that the endogenous expression of most RAR and RXR isotypes is readily detected. While the nuclear receptor co-repressors are highly expressed, two of the three nuclear receptor co-activators and the enzymes involved in RA synthesis are expressed at low level or undetectable, suggesting that the RA signaling pathway may be repressed in myogenic progenitors. Using the alpha-myosin heavy chain promoter-driven reporter (MyHC-GLuc), we have demonstrated that either ATRA or 9CRA is able to effectively induce myogenic differentiation, which can be synergistically enhanced when both ATRA and 9CRA are used. Upon ATRA and 9CRA treatment of C2C12 cells the expression of late myogenic markers significantly increases. We have further shown that adenovirus-mediated exogenous expression of RAR alpha and/or RXR a is able to effectively induce myogenic differentiation in a ligand-independent fashion. Morphologically, ATRA- and 9CRA-treated C2C12 cells exhibit elongated cell body and become multi-nucleated myoblasts, and even form myoblast fusion. Ultrastructural analysis under transmission electron microscope reveals that RA-treated myogenic progenitor cells exhibit an abundant presence of muscle fibers. Therefore, our results strongly suggest that RA signaling may play an important role in regulating myogenic differentiation. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

引用

页码：195 / 204

页数：10

共 56 条

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