Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6

被引:196
作者
Friedman, Michael S.
Long, Michael W.
Hankenson, Kurt D.
机构
[1] Univ Michigan, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Unit Lab Anim Medicinem, Ann Arbor, MI 48109 USA
关键词
mesenchymal stem cell; bone morphogenetic protein; BMP-6; osterix; human;
D O I
10.1002/jcb.20719
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bone marrow-derived mesenchymal stem cells (MSC) are multipotent, self-renewing, mesodermal-origin stem cells that are sequestered in the endosteal compartment. MSC are maintained in a relative state Of quiescence in vivo but in response to a variety of physiological and pathological stimuli, proliferate and differentiate into osteoblasts, chondrocytes, adipocytes, or hematopoiesis-supporting stromal cells. Little is understood regarding the cellular or molecular events underlying MSC fate decisions. We report that human MSC (hMSC) Cultured in defined, serum-free conditions respond to a narrow spectrum Of growth factors with osteogenic commitment, differentiation, and hydroxyapatite deposition. Of the osteogenic factors we examined, only treatment with bone morphogenetic protein (BMP) results in osteoinduction under defined serum-free conditions. Among BMP-2, 4, 6, and 7, BMP-6 is the most consistent and potent regulator of osteoblast differentiation and, of these BMPs, only BMP-6 gene expression is detected prior to hMSC osteoblast differentiation. Addition of exogenous BMP-6 to hMSC induces the expression or Upregulation of a repertoire of osteoblast-related genes including type I collagen, osteocalcin, bone sialoprotein, and their regulatory transcription factors Cbfa1/Runx2, and Osterix. This translates into increased production of osteogenic extracellular matrix (ECM) with subsequent hydroxyapatite deposition.
引用
收藏
页码:538 / 554
页数:17
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