title: 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.affiliation: From the Departments of Neuroscience and Regenerative Medicine, Wuhan University, Wuhan 430072, China, and.
authors.forename: Guodong
authors.initials: G
authors.lastname: Pan
authors.affiliation: the Grand Forks Human Nutrition Research Center, United States Department of Agriculture Agricultural Research Service, Grand Forks, North Dakota 58203.
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine.
authors.forename: Nianlan
authors.initials: N
authors.lastname: Yang
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine.
authors.forename: Kehong
authors.initials: K
authors.lastname: Ding
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.affiliation: Cellular Biology and Anatomy, and.
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine, Orthopaedic Surgery,Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.affiliation: From the Departments of Neuroscience and Regenerative Medicine, Orthopaedic Surgery,Georgia Regents University, Augusta, Georgia 30912, xshi@gru.edu.
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Shi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D000076182:Sp7 Transcription Factor; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C498608:Dsip1 protein, mouse; D047495:PPAR gamma; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors
keywords: Arthritis; Glucocorticoid; Inflammation; Osteoblast; Osteoporosis