LABORATORY AND ANIMAL STUDIES

Nonsteroidal Anti-inflammatory Drugs Induce Adipogenesis in Murine Pluripotent Stem Cells
JK Chang, ML Ho, CH Yeh, PY Chang, GJ Wang
Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

Steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) have been indicated to suppressive bone remodeling. Our previous results showed that NSAIDs suppressed proliferation and induced cell death in cultured osteoblasts and pluripotent stem cells (D1-cells), suggesting these effects might be one the mechanisms contributing to their inhibitory effects on bone remodeling in vivo. On the other hand, our previous results indicated that dexamethasone treatment shifts the characteristics of osteogenesis into adipogenesis in D1-cell. However, the influences of NSAID on adipogenesis in pluripotent stem cells were rarely investigated. In this study, we tested the adipogenesis of D1-cell upon long-term treatment of NSAIDs. NSAID influence on the osteocalcin expression of D1-cell was also examined. Indomethacin, ketorolac, diclofenac and piroxicam (10-5 and 10-4 M) were treated for 2, 4, 6 or 8 days after cell confluence. Lipid droplets in cultures were detected by oil red staining. Adipsin and osteocalcin mRNA expressions were examined by RT-PCR. In this study, we found that 10-4M of NSAID treatment for 4-8 days also induced adipogenesis in D1-cells, while shorter duration and lower concentration did not. Mild adipogenesis also occurred in cultures treated with 10-5M of indomethacin for 6 or 8 days, revealing the strongest effect among the 4 NSAIDs. Piroxicam revealed less effect on adipogenesis in D1-cells. However, despite of 2-day treatment of 10-5M indomethacin, NSAIDs did not affect the expressions of osteocalcin either at 10-5-10-4M or during 2-8 days of treatments. These results suggest that high dose and long term administration of NSAIDs may induce adipogenesis in pluripotent stem cells.