Tscheudschilsuren, G. and Bosserhoff, A. K. and Schlegel, J. and Vollmer, D. and Anton, A. and Alt, V. and Schnettler, R. and Brandt, J. and Proetzel, G. (2006) Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA. Experimental cell research 312 (1), pp. 63-72.
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Melanoma inhibitory activity (MIA), also referred to as cartilage-derived 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 C3H10T1/2, stimulating cell migration significantly at concentrations from 0.24 to 240 ng/ml, while inhibiting cell migration at higher doses of 2.4 microg/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 II 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.
|Date:||1 January 2006|
|Institutions:||Medicine > Lehrstuhl für Pathologie|
|Keywords:||MIA; CD-RAP; BMP; TGF-beta; Growth factor; Differentiation; Stem cell; Cartilage; Chondrocyte; Extracellular matrix; Chemotaxis; Gene expression|
|Subjects:||500 Science > 570 Life sciences|
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||30 Mar 2007|
|Last Modified:||20 Jul 2011 21:05|