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) gamma 2 and CCAAT/enhancer binding protein (C/EBP) a mRNA during adipogenesis was inhibited by compressive force, whereas C/EBP beta and C/EBP delta mRNA levels were unaffected. In preadipocytes, compressive force increased mRNA levels of Kruppel-like factor 2, preadipocyte factor 1, WNT10b, and cyclooxygenase-2 (COX-2) which are known as negative regulators for the PPAR gamma 2 and C/EBP alpha 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 PPAR gamma 2 and C/EBP alpha in a COX-2-dependent manner. (C) 2009. The Society for Biotechnology, Japan. All rights reserved.