Menin expression modulates mesenchymal cell commitment to the myogenic and osteogenic lineages

被引:31
作者
Aziz, Arif [1 ]
Miyake, Tetsuaki [1 ]
Engleka, Kurt A. [2 ,3 ]
Epstein, Jonathan A. [2 ,3 ]
McDermott, John C. [1 ]
机构
[1] York Univ, Dept Biol, LSB, N York, ON M3J 1P3, Canada
[2] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
[3] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
Menin; Myogenesis; BMP-2; TGF-beta; Mesenchymal; TRANSFORMING-GROWTH-FACTOR; BONE MORPHOGENETIC PROTEIN-2; MULTIPLE ENDOCRINE NEOPLASIA; SKELETAL-MUSCLE DIFFERENTIATION; FACTOR-BETA; GENE-EXPRESSION; OSTEOBLAST DIFFERENTIATION; TYPE-1; GENE; STEM-CELLS; MYOBLASTS;
D O I
10.1016/j.ydbio.2009.05.555
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Menin plays an established role in the differentiation of mesenchymal cells to the osteogenic lineage. Conversely, whether Menin influences the commitment of mesenschymal cells to the myogenic lineage, despite expression in the developing somite was previously unclear. We observed that Menin is down-regulated in C2C12 and C3H10T1/2 mesenchymal cells when muscle differentiation is induced. Moreover, maintenance of Menin expression by constitutive ectopic expression inhibited muscle cell differentiation. Reduction of Menin expression by siRNA technology results in precocious muscle differentiation and concomitantly attenuates BMP-2 induced osteogenesis. Reduced Menin expression antagonizes BMP-2 and TGF-beta 1 mediated inhibition of myogenesis. Furthermore, Menin was found to directly interact with and potentiate the transactivation properties of Smad3 in response to TGF-beta 1. Finally in concert with these observations, tissue-specific inactivation of Men1 in Pax3-expressing somite precursor cells leads to a patterning defect of rib formation and increased Muscle mass in the intercostal region. These data invoke a pivotal role for Menin in the competence of mesenchymal cells to respond to TGF-beta 1 and BMP-2 signals. Thus, by modulating cytokine responsiveness Menin functions to alter the balance of multipotent mesenchymal cell commitment to the osteogenic or myogenic lineages. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:116 / 130
页数:15
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