Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition

Guodong Pan, Jay Cao, Nianlan Yang, Kehong Ding, Cheng Fan, Wen Cheng Xiong, Mark Hamrick, Carlos M. Isales, Xing Ming Shi

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Glucocorticoids (GCs) have both anabolic and catabolic effects on bone. However, no GC anabolic effect mediator has been identified to date. Here we show that targeted expression of glucocorticoid-induced leucine zipper (GILZ), a GC anti-inflammatory effect mediator, enhances bone acquisition in mice. Transgenic mice, in which the expression of GILZ is under the control of a 3.6-kb rat type I collagen promoter, exhibited a high bone mass phenotype with significantly increased bone formation rate and osteoblast numbers. The increased osteoblast activity correlates with enhanced osteogenic differentiation and decreased adipogenic differentiation of bone marrow stromal cell cultures in vitro. In line with these changes, them RNA levels of key osteogenic regulators (Runx2 and Osx) increased, and the level of adipogenic regulator peroxisome proliferator-activated receptor (PPAR) γ2 decreased significantly. We also found that GILZ physically interacts with C/EBPs and disrupts C/EBP-mediated PPARγ gene transcription. In conclusion, our results showed that GILZ is capable of increasing bone acquisition in vivo, and this action is mediated via a mechanism involving the inhibition of PPARγ gene transcription and shifting of bone marrow MSC/progenitor cell lineage commitment in favor of the osteoblast pathway.

Original languageEnglish (US)
Pages (from-to)19373-19382
Number of pages10
JournalJournal of Biological Chemistry
Volume289
Issue number28
DOIs
StatePublished - Jul 11 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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