PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells

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 receptors gamma(PPAR gamma) 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, PPAR gamma may be a valuable target for drugs intended to enhance bone mass. However, little direct evidence is available for the role played by PPAR gamma in human mesenchymal lineage allocation. In this study, using human MSCs as an in vitro model, we showed that the two isoforms of PPAR gamma, PPAR gamma 1 and PPAR gamma 2, were differentially induced during hMSC adipogenesis, whereas only PPAR gamma 1 was detected during osteogenesis. BADGE and GW9662, two potential antagonists of PPAR gamma, as well as lentivirus-mediated knockdown of PPAR gamma, inhibited hMSC adipogenesis but did not significantly affect osteogenesis. PPAR gamma knockdown did not significantly influence the expression level of the osteogenic transcription factor Runx2. Together, these results suggest that PPAR gamma is not the master factor regulating mesenchymal lineage determination in human bone marrow. (C) 2011 Elsevier Ltd. All rights reserved.