title: PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are the common progenitors of osteoblasts and adipocytes. A reciprocal relationship exists between osteogenesis and adipogenesis in the bone marrow, and the identification of signaling pathways that stimulate MSC osteogenesis at the expense of adipogenesis is of great importance from the viewpoint of developing new therapeutic treatments for bone loss. The adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) has been reported to play a vital role in modulating mesenchymal lineage allocation within the bone marrow compartment, stimulating adipocyte development at the expense of osteoblast differentiation. Hence, PPARγ may be a valuable target for drugs intended to enhance bone mass. However, little direct evidence is available for the role played by PPARγ in human mesenchymal lineage allocation. In this study, using human MSCs as an in vitro model, we showed that the two isoforms of PPARγ, PPARγ1 and PPARγ2, were differentially induced during hMSC adipogenesis, whereas only PPARγ1 was detected during osteogenesis. BADGE and GW9662, two potential antagonists of PPARγ, as well as lentivirus-mediated knockdown of PPARγ, inhibited hMSC adipogenesis but did not significantly affect osteogenesis. PPARγ knockdown did not significantly influence the expression level of the osteogenic transcription factor Runx2. Together, these results suggest that PPARγ is not the master factor regulating mesenchymal lineage determination in human bone marrow.
authors: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, 74# Zhongshan Road 2, Guangzhou, Guangdong 510080, PR China.
authors: Wei-Hua
authors: WH
authors: Yu
authors: Fu-Gui
authors: FG
authors: Li
authors: Xiao-Yong
authors: XY
authors: Chen
authors: Jian-Tao
authors: JT
authors: Li
authors: Yan-Heng
authors: YH
authors: Wu
authors: Li-Hua
authors: LH
authors: Huang
authors: Zhen
authors: Z
authors: Wang
authors: Panlong
authors: P
authors: Li
authors: Tao
authors: T
authors: Wang
authors: Bruce T
authors: BT
authors: Lahn
authors: Andy Peng
authors: AP
authors: Xiang
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D047495:PPAR gamma; D034741:RNA, Small Interfering; D014157:Transcription Factors