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

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, the mRNA 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.

• Authors: Guodong Pan, Jay Cao, Nianlan Yang, Kehong Ding, Cheng Fan, Wen-Cheng Xiong, Mark Hamrick, Carlos M Isales, Xing-Ming Shi
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 28 Pg. 19373-82 (Jul 11 2014) ISSN: 1083-351X [Electronic] United States
• PMID: 24860090 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Core Binding Factor Alpha 1 Subunit
• Dsip1 protein, mouse
• PPAR gamma
• Runx2 protein, mouse
• Sp7 Transcription Factor
• Sp7 protein, mouse
• Transcription Factors

Topics

• Animals
• Bone Marrow Cells (cytology, metabolism)
• Core Binding Factor Alpha 1 Subunit (biosynthesis, genetics)
• Gene Expression Regulation (physiology)
• Male
• Mice
• Mice, Transgenic
• Osteoblasts (cytology, metabolism)
• Osteogenesis (physiology)
• PPAR gamma (genetics, metabolism)
• Promoter Regions, Genetic (physiology)
• Rats
• Sp7 Transcription Factor
• Stem Cells (cytology, metabolism)
• Transcription Factors (biosynthesis, genetics)
• Transcription, Genetic (physiology)