| Thrombospondin-2 is an endogenous adipocyte inhibitor. | |
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MedLine Citation:
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PMID: 20561899 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The matricellular protein thrombospondin-2 (TSP2) inhibits proliferation and enhances osteoblastogenesis of multipotent mesenchymal progenitor cells (MPC). Osteoblastogenesis and adipogenesis are reciprocally regulated, thus we hypothesized that TSP2 could be an inhibitor of adipogenesis. TSP2 gene expression is up-regulated during MPC osteoblast differentiation and down-regulated during adipogenic differentiation through a cAMP-PKA pathway, relative to control cells. Next, the importance of TSP2 in adipogenesis was studied by comparing gene-targeted knockout mice that lack TSP2 protein (TSP2-null) and control wild-type mice. TSP2-null marrow-derived MPC show 25% increased adipocytes. Similarly, TSP2-null adipose-derived MPC show increased adipocytes (25-50%) and proliferation (2-fold) relative to wild-type cells. However, the increase in TSP2-null adipocytes is not due to an increase in MPC number, because the percentage of adipocytes relative to total MPC is still significantly increased. Surprisingly, there are only minor alterations in the adipogenic transcriptional program (PPARγ and C/EBPα expression). Weight gain over time was evaluated in TSP2-null and control wild-type mice fed normal and high-fat diets. Female TSP2-null mice are 30% heavier than wild-type controls due to an increase in non-visceral adipose tissue, measured by dual-energy X-ray absorptiometry (DEXA) and direct weighing of fat pads. These results show that TSP2 is an endogenous matricellular protein produced by MPC that in addition to enhancing osteoblastogenesis, inhibits adipocytes and decreases subcutaneous adiposity. |
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Authors:
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Hailu S Shitaye; Shawn P Terkhorn; Jason A Combs; Kurt D Hankenson |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-31 |
Journal Detail:
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Title: Matrix biology : journal of the International Society for Matrix Biology Volume: 29 ISSN: 1569-1802 ISO Abbreviation: Matrix Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2011-01-24 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9432592 Medline TA: Matrix Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 549-56 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved. |
Affiliation:
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Medical Scientist Training Program, School of Medicine, University of Michigan, Michigan, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Absorptiometry, Photon
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methods Adipocytes / metabolism* Adipogenesis / physiology* Animals CCAAT-Enhancer-Binding Protein-alpha / metabolism Cell Differentiation Female Gene Expression Regulation / genetics Intra-Abdominal Fat / metabolism Mice Mice, Knockout Obesity / genetics Osteogenesis / physiology* PPAR gamma / metabolism Subcutaneous Fat / metabolism Thrombospondins / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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P30 DK019525-32/DK/NIDDK NIH HHS; R01 AR049682/AR/NIAMS NIH HHS; R01 AR049682-06/AR/NIAMS NIH HHS; R01 AR054714/AR/NIAMS NIH HHS; R01 AR054714-05/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CCAAT-Enhancer-Binding Protein-alpha; 0/PPAR gamma; 0/Thrombospondins; 0/thrombospondin 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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