title: Negative regulation of adipogenesis from human mesenchymal stem cells by Jun N-terminal kinase.
abstract: Human mesenchymal stem cells (hMSCs) are capable of differentiating into several cell types including adipocytes, osteoblasts, and chondrocytes, under appropriate culture conditions. We found that SP600125, an inhibitor of Jun N-terminal kinase (JNK), promoted adipogenesis whereas it repressed osteogenesis from hMSCs. SP600125 increased the expression of adipogenic transcription factors, CCAAT/enhancer-binding proteins alpha and beta as well as peroxisome proliferator-activated receptor gamma2, which suggested that the chemical acted on the early steps of transcriptional regulatory cascade in adipogenesis. A gene reporter assay showed that SP600125 and a dominant negative JNK promoted a transcriptional activity dependent on the cAMP-response element (CRE). Thus, JNK represses adipogenesis from hMSCs probably by, at least in part, inhibiting the transactivating function of CRE-binding protein. Another action of JNK, phosphorylation at Ser(307) of insulin receptor substrate-1, was also predicted to contribute to the repression of adipogenesis.
authors.affiliation: Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tominaga
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000873:Anthracenes; D015415:Biomarkers; D004791:Enzyme Inhibitors; D010768:Phosphoserine; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases