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Pioglitazone and dexamethasone induce adipogenesis in D1 bone marrow stromal cell line, but not through the peroxisome proliferator-activated receptor-γ pathway
- Source :
- Life Sciences. 82:561-569
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Osteoblasts and adipocytes share a common progenitor in bone marrow. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical role in adipogenesis. Using a mouse pluripotent mesenchymal cell, D1, as a model, several reports have demonstrated that dexamethasone, a glucocorticoid, can induce adipogenesis. We first examined whether adipogenesis induction in D1 cells is initiated by activation of PPAR-gamma. The results revealed that pioglitazone induces adipogenesis in D1 cells in a dose-dependent manner and decreases alkaline phosphatase activity in D1 cells. Interestingly, this adipogenesis was not blocked by bisphenol A diglycidyl ether, a PPAR-gamma antagonist. A PPAR-gamma-mediated reporter gene assay showed no response to pioglitazone. We then asked whether dexamethasone-induced adipogenesis can be repressed by mifepristone (RU486), an antagonist of glucocorticoid receptor. The results disclosed that mifepristone cannot counteract dexamethasone-induced adipogenesis, and mifepristone itself induced adipogenesis in D1 cells. Moreover, glucocorticoid receptor-mediated reporter gene assay was not responsive to dexamethasone or mifepristone. We concluded that the adipogenesis induced by pioglitazone and dexamethasone in D1 cells may not occur via a PPAR-gamma and glucocorticoid receptor pathway. Finally, we analyzed the gene expression profile of D1 by cDNA microarray after treatment with dexamethasone. We found that the expression of several adipogenesis-related genes is highly provoked by this agent.
- Subjects :
- Pluripotent Stem Cells
medicine.medical_specialty
Peroxisome proliferator-activated receptor
Bone Marrow Cells
Dexamethasone
General Biochemistry, Genetics and Molecular Biology
Cell Line
Mice
Hormone Antagonists
Receptors, Glucocorticoid
Glucocorticoid receptor
Genes, Reporter
Internal medicine
medicine
Animals
Hypoglycemic Agents
Cell Lineage
General Pharmacology, Toxicology and Pharmaceutics
Receptor
Glucocorticoids
Oligonucleotide Array Sequence Analysis
chemistry.chemical_classification
Mice, Inbred BALB C
Reporter gene
Adipogenesis
Dose-Response Relationship, Drug
Pioglitazone
Chemistry
Gene Expression Profiling
Mesenchymal stem cell
General Medicine
Mifepristone
Surgery
PPAR gamma
Endocrinology
Gene Expression Regulation
Thiazolidinediones
Stromal Cells
Glucocorticoid
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....35d5c656fcf816004c207bb3f082db8d