Pioglitazone and dexamethasone induce adipogenesis in D1 bone marrow stromal cell line, but not through the peroxisome proliferator-activated receptor-gamma pathway.
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.
Hung
Shao-Hung
SH
Orthopedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yeh
Ching-Hua
CH
Huang
Hsuan-Ti
HT
Wu
Peihua
P
Ho
Mei-Ling
ML
Chen
Chung-Hwan
CH
Wang
Chihuei
C
Chao
David
D
Wang
Gwo-Jaw
GJ
D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism*; D000077205:Pioglitazone; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D045162:Thiazolidinediones; D015735:Mifepristone; D003907:Dexamethasone; D000077205:Pioglitazone