Reciprocal roles of Msx2 in regulation of osteoblast and adipocyte differentiation
Reciprocal roles of Msx2 in regulation of osteoblast and adipocyte differentiation
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DOI：
10.1074/jbc.m403621200
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发表时间：
2004-08-06
影响因子：
4.8
通讯作者：
Yoneda, T
中科院分区：
文献类型：
--
作者：
Ichida, F;Nishimura, R;Yoneda, T
Msx 2基因缺陷的小鼠表现出颅骨骨化缺陷和与成骨细胞数量减少相关的骨形成显著减少，从而表明Msx 2参与骨形成。然而，Msx 2在成骨细胞分化过程中的确切作用尚未完全了解。在本研究中，我们研究了Msx 2在多能间充质细胞系C3 H10 T12和C2 C12以及小鼠原代成骨细胞中调节成骨细胞分化的作用。Msx 2的导入诱导了C3 H10 T12和C2 C12细胞中碱性磷酸酶的活性，并促进了小鼠原代成骨细胞的钙化。在从Runx 2缺陷小鼠分离的间充质细胞中也观察到Msx 2的这种作用。有趣的是，Msx 2的表达诱导骨形态发生蛋白2处理Runx 2缺陷的间充质细胞。相比之下，Msx 2减少过氧化物酶体增殖物激活受体γ（PPARgamma）的表达和前脂肪细胞系3 T3-F442 A的脂肪形成。此外，Msx 2抑制PPARgamma、CCAAT/增强子结合蛋白β（C/EBP β）和C/EBP δ的转录活性，并阻断由PPARgamma、C/EBP α、C/EBP β或C/EBP δ过表达诱导的间充质细胞的脂肪细胞分化。这些数据表明，Msx 2促进成骨细胞分化独立于Runx 2，并通过抑制PPARgamma和C/EBP家族负调节脂肪细胞分化。
Mice deficient in the Msx2 gene manifest defects in skull ossification and a marked reduction in bone formation associated with decreases in osteoblast numbers, thus suggesting that Msx2 is involved in bone formation. However, the precise role of Msx2 during osteoblast differentiation is not fully understood. In the present study, we investigated the role of Msx2 in the regulation of osteoblast differentiation in the multipotent mesenchymal cell lines C3H10T1/2 and C2C12 and in murine primary osteoblasts. Introduction of Msx2 induced alkaline phosphatase activity in C3H10T1/2 and C2C12 cells and promoted the calcification of murine primary osteoblasts. This effect of Msx2 was also observed in mesenchymal cells isolated from Runx2-deficient mice. Interestingly the expression of Msx2 was induced by bone morphogenetic protein 2 treatment in Runx2-deficient mesenchymal cells. In contrast, Msx2 diminished peroxisome proliferator-activated receptor gamma (PPARgamma) expression and adipogenesis of the preadipocytic cell line 3T3-F442A. Moreover Msx2 inhibited the transcriptional activity of PPARgamma, CCAAT/enhancer-binding protein beta (C/EBPbeta), and C/EBPdelta and blocked adipocyte differentiation of mesenchymal cells induced by overexpression of PPARgamma, C/EBPalpha, C/EBPbeta, or C/EBPdelta. These data indicate that Msx2 promotes osteoblast differentiation independently of Runx2 and negatively regulates adipocyte differentiation through inhibition of PPARgamma and the C/EBP family.