HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 8, 4723-4729, February 22, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/8/4723    most recent M704147200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, W. Articles by Shi, X.-M. Search for Related Content PubMed PubMed Citation Articles by Zhang, W. Articles by Shi, X.-M. Social Bookmarking                      What's this?

Regulation of Mesenchymal Stem Cell Osteogenic Differentiation by Glucocorticoid-induced Leucine Zipper (GILZ)^*

Weixi Zhang¹, Nianlan Yang^¶1, and Xing-Ming Shi^||2

From the Institute of Molecular Medicine and Genetics and the Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, the ^¶Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, China, and the ^||Department of Pathology, Medical College of Georgia, Augusta, Georgia 30912

Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages, including osteoblasts and adipocytes. We reported previously that glucocorticoid-induced leucine zipper (GILZ) inhibits peroxisome proliferator-activated receptor -2 (Ppar2) expression and blocks adipocyte differentiation. Here we show that overexpression of GILZ in mouse MSCs, but not MC3T3-E1 osteoblasts, increases alkaline phosphatase activity and enhances mineralized bone nodule formation, whereas knockdown of Gilz reduces MSC osteogenic differentiation capacity. Consistent with these observations, real-time reverse transcription-PCR analysis showed that both basal and differentiation-induced transcripts of the lineage commitment gene Runx2/Cbfa1, as well as osteoblast differentiation marker genes including alkaline phosphatase, type I collagen, and osteocalcin, were all increased in GILZ-expressing cells. In contrast, the mRNA levels of adipogenic Ppar2 and C/ebp were significantly reduced in GILZ-expressing cells under both osteogenic and adipogenic conditions. Together, our results demonstrate that GILZ functions as a modulator of MSCs and that overexpression of GILZ shifts the balance between osteogenic and adipogenic differentiation of MSCs toward the osteogenic pathway. These data suggest that GILZ may have therapeutic value for stem cell-based therapies of metabolic bone diseases, such as fracture repair.

Received for publication, May 21, 2007 , and in revised form, December 12, 2007.

^* This work was supported by grants from the American Heart Association. 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.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Institute of Molecular Medicine and Genetics and Dept. of Pathology, Medical College of Georgia, 1120 15th St., CB-2803, Augusta, GA 30912. Tel.: 706-721-1097; Fax: 706-721-0340; E-mail: xshi{at}mcg.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?