Compressive force inhibits adipogenesis through COX-2-mediated down-regulation of PPARgamma2 and C/EBPalpha.

Various mechanical stimuli affect differentiation of mesoderm-derived cells such as osteoblasts or myoblasts, suggesting that adipogenesis may also be influenced by mechanical stimulation. However, effects of mechanical stimuli on adipogenesis are scarcely known. Compressive force was applied to a human preadipocyte cell line, SGBS. Levels of gene expression were estimated by real-time reverse transcription-polymerase chain reaction. The accumulation of lipids was evaluated by Sudan III or Oil Red O staining. In SGBS cells subjected to a compressive force of 226 Pa for 12 h before adipogenic induction, adipogenesis was inhibited. Compressive force immediately after adipogenic induction did not affect the adipogenesis. The expression of peroxisome proliferator-activated receptor (PPAR) gamma2 and CCAAT/enhancer binding protein (C/EBP) alpha mRNA during adipogenesis was inhibited by compressive force, whereas C/EBPbeta and C/EBPdelta mRNA levels were unaffected. In preadipocytes, compressive force increased mRNA levels of Krüppel-like factor 2, preadipocyte factor 1, WNT10b, and cyclooxygenase-2 (COX-2) which are known as negative regulators for the PPARgamma2 and C/EBPalpha genes. Furthermore, a COX-2 inhibitor completely reversed the inhibition of adipogenesis by compressive force. In conclusion, compressive force inhibited adipogenesis by suppressing expression of PPARgamma2 and C/EBPalpha in a COX-2-dependent manner. Copyright 2009. Published by Elsevier B.V.