Upregulation of Runx2 and Osterix during in vitro chondrogenesis of human adipose-derived stromal cells

被引:37
作者
Rich, Jason T. [6 ]
Rosova, Ivana [5 ]
Nolta, Jan A. [4 ]
Myckatyn, Terence M. [3 ]
Sandell, Linda J. [1 ,2 ]
McAlinden, Audrey [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Div Plast & Reconstruct Surg, St Louis, MO 63110 USA
[4] Univ Calif Davis, Dept Internal Med, Stem Cell Program, Davis, CA 95616 USA
[5] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA
[6] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA
关键词
human adipose-derived stromal cells; (HADSC); mesenchymal stromal cell (MSC); mesenchymal stem cells; in vitro differentiation; chondrogenesis; TGF-beta; 3; transcription factors; Runx2; Osterix;
D O I
10.1016/j.bbrc.2008.05.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The aim of this study was to create a gene expression profile to better define the phenotype of human adipose-derived stromal cells (HADSCs) during in vitro chondrogenesis, osteogenesis and adipogenesis. A novel aspect of this work was the analysis of the same subset of genes during HADSC differentiation into all three lineages. Chondrogenic induction resulted in increased mRNA expression of Sox transcription factors, COL2A1, COL10A1, Runx2, and Osterix. This is the first report demonstrating significant upregulation in expression of osteogenesis-related transcription factors Runx2 and Osterix by TGF-beta 3 induction of HADSCs during in vitro chondrogenesis. These findings suggest that the commonly-used chondrogenic induction reagents promote differentiation suggestive of hypertrophic chondrocytes and osteoblasts. We conclude that alternative strategies are required to induce efficient articular chondrocyte differentiation in order for HADSCs to be of clinical use in cartilage tissue engineering. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:230 / 235
页数:6
相关论文
共 34 条
[1]
The transcrintion factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6 [J].
Akiyama, H ;
Chaboissier, MC ;
Martin, JF ;
Schedl, A ;
de Crombrugghe, B .
GENES & DEVELOPMENT, 2002, 16 (21) :2813-2828
[2]
Effects of transforming growth factor β1 and dexamethasone on the growth and chondrogenic differentiation of adipose-derived stromal cells [J].
Awad, HA ;
Halvorsen, YDC ;
Gimble, JM ;
Guilak, F .
TISSUE ENGINEERING, 2003, 9 (06) :1301-1312
[3]
Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds [J].
Awad, HA ;
Wickham, MQ ;
Leddy, HA ;
Gimble, JM ;
Guilak, F .
BIOMATERIALS, 2004, 25 (16) :3211-3222
[4]
Chondrogenic differentiation of mesenchymal stem cells from bone marrow: Differentiation-dependent gene expression of matrix components [J].
Barry, F ;
Boynton, RE ;
Liu, BS ;
Murphy, JM .
EXPERIMENTAL CELL RESEARCH, 2001, 268 (02) :189-200
[5]
Differentiation of bone marrow stroma-derived mesenchymal cells [J].
Benayahu, D. ;
Akavia, U. D. ;
Shur, I. .
CURRENT MEDICINAL CHEMISTRY, 2007, 14 (02) :173-179
[6]
Sox9 is required for cartilage formation [J].
Bi, WM ;
Deng, JM ;
Zhang, ZP ;
Behringer, RR ;
de Crombrugghe, B .
NATURE GENETICS, 1999, 22 (01) :85-89
[7]
Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9 [J].
Cucchiarini, Magali ;
Thurn, Tanja ;
Weimer, Anja ;
Kohn, Dieter ;
Terwilliger, Ernest F. ;
Madry, Henning .
ARTHRITIS AND RHEUMATISM, 2007, 56 (01) :158-167
[8]
Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6 [J].
Estes, BT ;
Wu, AW ;
Guilak, F .
ARTHRITIS AND RHEUMATISM, 2006, 54 (04) :1222-1232
[9]
Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes [J].
Fukui, N ;
Zhu, Y ;
Maloney, WJ ;
Clohisy, J ;
Sandell, LJ .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2003, 85A :59-66
[10]
Adipose-derived adult stem cells: isolation, characterization, and differentiation potential [J].
Gimble, JM ;
Guilak, F .
CYTOTHERAPY, 2003, 5 (05) :362-369