![]()
|
|
||||||||
J. Biol. Chem., Vol. 280, Issue 24, 22688-22696, June 17, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
/Smad3 Signaling*



¶
From the
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115 and the
Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213
Although hypoxia and transforming growth factor-
(TGF-
) inhibit differentiation of adipocytes from preadipocytes and bone marrow-derived cells in several species, the relationship between hypoxia and TGF-
signaling in adipocytogenesis is unknown. In this study, we evaluated the mechanisms of inhibition of adipocyte differentiation by hypoxia and TGF-
in human and murine marrow stromal cells (MSCs) and the role of TGF-
/Smad signaling in the inhibition of adipocytogenesis by hypoxia. Both hypoxia-mimetic deferoxamine mesylate (DFO) and TGF-
1 inhibited adipocyte differentiation (1.0% versus the control at 15 µM DFO and 1.4% versus the control at 1 ng/ml TGF-
1) and adipocyte gene expression (peroxisome proliferator-activated receptor-
2 and lipoprotein lipase) in human MSCs after 21 days of treatment. Hypoxia (2% O2) and DFO (but not TGF-
1) increased hypoxia-inducible factor-1
as shown by Western blotting. Macroarrays and Western and Northern blot analyses showed that hypoxia activated the TGF-
/Smad signaling pathway and that both hypoxia and TGF-
1 modulated adipocyte differentiation pathways such as the insulin-, peroxisome proliferator-activated receptor-
-, phosphatidylinositol 3-kinase-, and MAPK-associated signaling pathways. Studies with mouse marrow stromal cell lines derived from Smad3+/+ or Smad3/ mice revealed that the TGF-
type I receptor (ALK-5) and its intracellular signaling molecule Smad3 were necessary for the inhibition of adipocyte differentiation by both TGF-
and hypoxia-mimetic DFO. Thus, the TGF-
/Smad signaling pathway is required for hypoxia-mediated inhibition of adipocyte differentiation in MSCs.
Received for publication, November 16, 2004 , and in revised form, March 25, 2005.
* This work was supported by Grants AR45870 and AG 025015 from the National Institutes of Health (to J. G.). This work was presented as a plenary poster at the 26th Annual Meeting of the American Society for Bone and Mineral Research, October 15, 2004, Seattle, WA. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Orthopedic Surgery, Brigham & Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115. Tel.: 617-732-5397; Fax: 617-732-6937; E-mail: jglowacki{at}rics.bwh.harvard.edu.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
B. Wang, I S. Wood, and P. Trayhurn Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes J. Endocrinol., July 1, 2008; 198(1): 127 - 134. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Guo, J. Flanagan, R. Jasuja, J. Kirkland, L. Jiang, and S. Bhasin The Effects of Myostatin on Adipogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells Are Mediated through Cross-communication between Smad3 and Wnt/{beta}-Catenin Signaling Pathways J. Biol. Chem., April 4, 2008; 283(14): 9136 - 9145. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Martin-Rendon, S. J.M. Hale, D. Ryan, D. Baban, S. P. Forde, M. Roubelakis, D. Sweeney, M. Moukayed, A. L. Harris, K. Davies, et al. Transcriptional Profiling of Human Cord Blood CD133+ and Cultured Bone Marrow Mesenchymal Stem Cells in Response to Hypoxia Stem Cells, April 1, 2007; 25(4): 1003 - 1012. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. R. Patel Shared genetic risk factors for obstructive sleep apnea and obesity J Appl Physiol, October 1, 2005; 99(4): 1600 - 1606. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Suzuki, G.-i. Kusakai, Y. Shimojo, J. Chen, T. Ogura, M. Kobayashi, and H. Esumi Involvement of Transforming Growth Factor-{beta}1 Signaling in Hypoxia-induced Tolerance to Glucose Starvation J. Biol. Chem., September 9, 2005; 280(36): 31557 - 31563. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |