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Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ).
J Biol Chem. 2008 Feb 22; 283(8):4723-9.JB

Abstract

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 gamma-2 (Ppargamma2) 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 Ppargamma2 and C/ebpalpha 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.

Authors+Show Affiliations

Institute of Molecular Medicine and Genetics, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18084007

Citation

Zhang, Weixi, et al. "Regulation of Mesenchymal Stem Cell Osteogenic Differentiation By Glucocorticoid-induced Leucine Zipper (GILZ)." The Journal of Biological Chemistry, vol. 283, no. 8, 2008, pp. 4723-9.
Zhang W, Yang N, Shi XM. Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). J Biol Chem. 2008;283(8):4723-9.
Zhang, W., Yang, N., & Shi, X. M. (2008). Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). The Journal of Biological Chemistry, 283(8), 4723-9.
Zhang W, Yang N, Shi XM. Regulation of Mesenchymal Stem Cell Osteogenic Differentiation By Glucocorticoid-induced Leucine Zipper (GILZ). J Biol Chem. 2008 Feb 22;283(8):4723-9. PubMed PMID: 18084007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). AU - Zhang,Weixi, AU - Yang,Nianlan, AU - Shi,Xing-Ming, Y1 - 2007/12/14/ PY - 2007/12/18/pubmed PY - 2008/4/11/medline PY - 2007/12/18/entrez SP - 4723 EP - 9 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 283 IS - 8 N2 - 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 gamma-2 (Ppargamma2) 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 Ppargamma2 and C/ebpalpha 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18084007/Regulation_of_mesenchymal_stem_cell_osteogenic_differentiation_by_glucocorticoid_induced_leucine_zipper__GILZ__ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=18084007 DB - PRIME DP - Unbound Medicine ER -