Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA
Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA
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DOI：
10.1016/j.yexcr.2005.09.017
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Proetzel, G
中科院分区：
文献类型：
--
作者：
Tscheudschilsuren, G;Bosserhoff, AK;Proetzel, G
黑色素瘤抑制活性(MIA)又称软骨抑制维甲酸敏感蛋白(CD-RAP)，是一种11 kDa的分泌型蛋白，主要在胚胎发育和成年期的软骨组织中表达。目前，MIA在软骨组织中的作用尚不清楚。在此，我们描述了MIA对间充质干细胞系C3HIOT1/2的趋化作用，在0.24-240 ng/ml的浓度下显著刺激细胞迁移，而在较高剂量2.4µg/ml时抑制细胞迁移。在分析MIA在分化过程中的作用时，我们发现MIA本身不能诱导小鼠或人的间充质干细胞分化。然而，MIA影响骨形态发生蛋白-2和转化生长因子-β3在骨髓间充质干细胞分化过程中的作用，在支持软骨细胞表型的同时抑制成骨分化。定量RT-PCR分析显示，与单独加入BMP-2和MIA相比，在MIA和转化生长因子-β3或骨形态发生蛋白-2诱导分化的人骨髓间充质干细胞(HMSC)中，软骨标记物MIA、11型胶原和聚集素表达上调。此外，MIA下调BMP-2处理的hMSC培养中骨桥蛋白和骨钙素的基因表达，抑制BMP-2的成骨潜力。在人类原代软骨细胞的情况下，MIA刺激细胞外基质沉积，增加糖胺多糖的含量。因此，我们推测MIA在软骨细胞分化和维持过程中起着重要的调节作用。(C)2005 Elsevier Inc.保留所有权利。
Melanoma inhibitory activity (MIA), also referred to as cartilage-detived retinoic acid-sensitive protein (CD-RAP), an 11-kDa secreted protein, is mainly expressed in cartilaginous tissue during embryogenesis and adulthood. Currently, the function of MIA in cartilage tissue is not understood. Here, we describe that MIA acts as a chemotactic factor on the mesenchymal stem cell line C3HIOT1/2, stimulating cell migration significantly at concentrations from 0.24 to 240 ng/ml, while inhibiting cell migration at higher doses of 2.4 mu g/ml. When analyzing the role of MIA during differentiation processes, we show that MIA by itself is not capable to induce the differentiation of murine or human mesenchymal stem cells. However, MIA influences the action of bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta 3 during mesenchymal stem cell differentiation, supporting the chondrogenic phenotype while inhibiting osteogenic differentiation. Quantitative RT-PCR analysis revealed the up-regulation of the cartilage markers MIA, collagen type 11 and aggrecan in human mesenchymal stem cell (HMSC) cultures differentiated in the presence of MIA and TGF-beta 3 or BMP-2 when compared to HMSC cultures differentiated in the presence of TGF-beta 3 or BMP-2 alone. Further, MIA down-regulates gene expression of osteopontin and osteocalcin in BMP-2 treated HMSC cultures inhibiting the osteogenic potential of BMP-2. In the case of human primary chondrocytes MIA stimulates extracellular matrix deposition, increasing the glycosaminoglycan content. Therefore, we postulate that MIA is an important regulator during chondrogenic differentiation and maintenance of cartilage. (c) 2005 Elsevier Inc. All rights reserved.