title: Osterix represses adipogenesis by negatively regulating PPARγ transcriptional activity.
abstract: Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). Further studies indicated that Osterix significantly decreased PPARγ-induced transcriptional activity. Using co-immunoprecipitation and GST-pull down analysis, we found that Osterix directly interacts with PPARγ. The ligand-binding domain (LBD) of PPARγ was responsible for this interaction, which was followed by repression of PPARγ-induced transcriptional activity, even in the presence of rosiglitazone. Taken together, we identified the Osterix has an important regulatory role on PPARγ activity, which contributed to the mechanism of adipogenesis.
authors.affiliation: College of Pharmacy &Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Han
authors.affiliation: College of Pharmacy &Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Chae Yul
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea.
authors.forename: Heesun
authors.initials: H
authors.lastname: Cheong
authors.affiliation: College of Pharmacy &Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D000076182:Sp7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D047495:PPAR gamma; D034741:RNA, Small Interfering; D000076182:Sp7 Transcription Factor