Objective: To explore the role of peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway in osteo- blast differentiation of rat bone marrow mesenchymal stem cells (BMSCs) cultured in simulated microgravity.
Methods: Rat BMSCs were cultured in simulated microgravity (by rotating clinostat) in the presence of 10 µmol/L pioglitazone, 10 µmol/L GW9662, or both pioglitazone and GW9662, with the cells cultured in normal gravity as the control group. After osteogenic induction for 14 days, the cells were stained with alizarin red for the bone nodules and with oil red-O for the fat cells, and the fat rate was calculated. ALP activity in the cells was determined in each group, and RT-PCR was performed to detect cellular expressions of PPARγ mRNA.
Results: Pioglitazone significantly inhibited osteoblast differentiation of the BMSCs, whereas GW9662 promoted the cell differentiation by suppressing the activation of PPARγ.
Conclusion: We hypothesize that the activation of PPARγ signaling pathway is one of the main mechanisms for inhibited osteoblast differentiation of rat BMSCs in simulated microgravity, and inhibiting PPARγ pathway activation can effectively prevent and treat microgravity-induced osteoporosis.