Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ)

Weixi Zhang, Nianlan Yang, Xing Ming Shi

Research output: Contribution to journalArticle

98 Citations (Scopus)

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 γ-2 (Pparγ2) 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 Pparγ2 and C/ebpα 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.

Original languageEnglish (US)
Pages (from-to)4723-4729
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
StatePublished - Feb 22 2008

Fingerprint

Leucine Zippers
Stem cells
Mesenchymal Stromal Cells
Glucocorticoids
Cell Differentiation
Osteoblasts
Peroxisome Proliferator-Activated Receptors
Adipocytes
Alkaline Phosphatase
Bone
Genes
Metabolic Bone Diseases
Osteocalcin
Differentiation Antigens
Cell Lineage
Transcription
Cell- and Tissue-Based Therapy
Collagen Type I
Osteogenesis
Modulators

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). / Zhang, Weixi; Yang, Nianlan; Shi, Xing Ming.

In: Journal of Biological Chemistry, Vol. 283, No. 8, 22.02.2008, p. 4723-4729.

Research output: Contribution to journalArticle

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