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BMP‐3 promotes mesenchymal stem cell proliferation through the TGF‐β/activin signaling pathway
Author(s) -
Stewart Aaron,
Guan Haiyan,
Yang Kaiping
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22064
Subject(s) - adipogenesis , mesenchymal stem cell , microbiology and biotechnology , activin type 2 receptors , bmpr2 , bone morphogenetic protein , transforming growth factor , cell growth , biology , signal transduction , adipocyte , cellular differentiation , chemistry , endocrinology , tgf beta signaling pathway , adipose tissue , biochemistry , gene
Adipogenesis plays a key role in the pathogenesis of obesity. It begins with the commitment of mesenchymal stem cells (MSCs) to the adipocyte lineage, followed by terminal differentiation of preadipocytes to mature adipocytes. A critical, but poorly understood, component of adipogenesis involves proliferation of MSCs and preadipocytes. The present study was undertaken to examine the hypothesis that bone morphogenetic protein‐3 (BMP‐3) promotes adipogenesis using C3H10T1/2 MSCs and 3T3‐L1 preadipocytes as in vitro model systems. We demonstrated that although it did not promote the commitment of MSCs to the adipocyte lineage or the differentiation of preadipocytes to adipocytes, BMP‐3‐stimulated proliferation by threefold in both cell types. Owing to a lack of information on MSC proliferation, we then delineated the molecular mechanisms underlying BMP‐3‐stimulated MSC proliferation. We showed that BMP‐3 activated the transforming growth factor‐β (TGF‐β)/activin but not ERK1/2, p38 MAPK, or JNK signaling pathways in C3H10T1/2 cells. Furthermore, the TGF‐β/activin receptor kinase inhibitor SB‐431542 blocked BMP‐3‐stimulated proliferation. Importantly, siRNA‐mediated knockdown of the key TGF‐β/activin signaling pathway components, ActRIIB, ALK4, or Smad2, abrogated the mitogenic effects of BMP‐3 on MSCs. Together, these results demonstrate that BMP‐3 stimulates MSC proliferation via the TGF‐β/activin signaling pathway, thus revealing a novel role for this divergent and poorly understood member of the TGF‐β superfamily in regulating MSC proliferation. J. Cell. Physiol. 223:658–666, 2010. © 2010 Wiley‐Liss, Inc.