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J Cell Mol Med. 2013 Sep;17(9):1188-93. doi: 10.1111/jcmm.12098. Epub 2013 Aug 13.

PPARγ silencing enhances osteogenic differentiation of human adipose-derived mesenchymal stem cells.

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  • 1Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis, and has been indicated as a potential therapeutic target to promote osteoblast differentiation. However, recent studies suggest that suppression of PPARγ inhibits adipogenesis, but does not promote osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs). It was reasoned that the osteogenic effect of PPARγ suppression may be masked by the strong osteogenesis-inducing condition commonly used, resulting in a high degree of matrix mineralization in both control and experimental groups. This study investigates the role of PPARγ in the lineage commitment of human adipose-derived mesenchymal stem cells (hADSCs) by interfering with the function of PPARγ mRNA through small interfering RNAs (siRNAs) specific for PPARγ2. By applying an osteogenic induction condition less potent than that used conventionally, we found that PPARγ silencing led to retardation of adipogenesis and stimulated a higher level of matrix mineralization. The mRNA level of PPARγ decreased to 47% of control 2 days after treatment with 50 nmol/l PPARγ2 siRNA, while its protein expression was 60% of mock control. In the meantime, osteogenic marker genes, including bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC), were up-regulated under PPARγ silencing. Our results suggest that transient suppression of PPARγ promotes the onset of osteogenesis, and may be considered a new strategy to stimulate bone formation in bone tissue engineering using hADSCs.

© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

KEYWORDS:

Human adipose tissue-derived mesenchymal stem cells; adipogenesis; osteogenesis; peroxisome proliferator-activated receptor gamma; small interfering RNA

PMID:
23937351
[PubMed - indexed for MEDLINE]
PMCID:
PMC4118177
Free PMC Article
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