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

Mon Juan Lee, Hui Ting Chen, Mei Ling Ho, Chung Hwan Chen, Shu Chun Chuang, Sung Cheng Huang, Yin Chih Fu, Gwo Jaw Wang, Lin Kang, Je Ken Chang

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1188-1193
Number of pages6
JournalJournal of Cellular and Molecular Medicine
Volume17
Issue number9
DOIs
Publication statusPublished - 2013 Sep

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

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