Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-2-18
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4723-9
pubmed:meshHeading
pubmed-meshheading:18084007-Adipocytes, pubmed-meshheading:18084007-Animals, pubmed-meshheading:18084007-Antigens, Differentiation, pubmed-meshheading:18084007-CCAAT-Enhancer-Binding Protein-alpha, pubmed-meshheading:18084007-Calcification, Physiologic, pubmed-meshheading:18084007-Cell Differentiation, pubmed-meshheading:18084007-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:18084007-Fractures, Bone, pubmed-meshheading:18084007-Gene Expression Regulation, pubmed-meshheading:18084007-Mesenchymal Stem Cells, pubmed-meshheading:18084007-Mice, pubmed-meshheading:18084007-Organ Specificity, pubmed-meshheading:18084007-Osteoblasts, pubmed-meshheading:18084007-Osteogenesis, pubmed-meshheading:18084007-PPAR gamma, pubmed-meshheading:18084007-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18084007-Transcription Factors
pubmed:year
2008
pubmed:articleTitle
Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ).
pubmed:affiliation
Institute of Molecular Medicine and Genetics, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't