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

Peroxisome proliferator-activated receptor gamma (PPAR) 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 PPAR 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 PPAR 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 PPAR in the lineage commitment of human adipose-derived mesenchymal stem cells (hADSCs) by interfering with the function of PPAR mRNA through small interfering RNAs (siRNAs) specific for PPAR2. By applying an osteogenic induction condition less potent than that used conventionally, we found that PPAR silencing led to retardation of adipogenesis and stimulated a higher level of matrix mineralization. The mRNA level of PPAR decreased to 47% of control 2days after treatment with 50nmol/l PPAR2 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 PPAR silencing. Our results suggest that transient suppression of PPAR promotes the onset of osteogenesis, and may be considered a new strategy to stimulate bone formation in bone tissue engineering using hADSCs.