Abstract
Introduction: Studies have shown steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) suppress bone remodeling. Previous results have indicated that NSAIDs suppress proliferation and induce cell death in cultured osteoblasts and pluripotent stem cells (D1-cells), suggesting these effects might be one of 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-cells. However, the influences of NSAID on adipogenesis in pluripotent stem cells have rarely been investigated. In this study, we tested the adipogenesis of D1-cells upon long-term treatment of NSAIDs. NSAID influence on the osteocalcin expressions of D1-cells was also examined.
Materials and Methods: The effects of treatments with indomethacin, ketorolac, diclofenac and piroxicam (10−5 and 10−4 M) for 2, 4 6 or 8 days were evaluated. Lipid droplets in cultures were detected by oil red staining. Adipsin and osteocalcin mRNA expressions were examined by RT-PCR.
Results: In this study, 10−4M of NSAID treatment for 4–8 days 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 effects on adipogenesis in D1-cells. However, despite 2-days of treatment with 10−5M indomethacin, NSAIDs did not affect the expression of osteocalcin either at 10−5–10−4M or during 2–8 days of treatments.
Conclusion: These results suggest that high dose and long term administration of NSAIDs may induce adipogenesis in pluripotent stem cells.
The abstracts were prepared by Michael A. Mont, M.D. and Lynne C. Jones, Ph.D. Correspondence should be addressed to L. Jones at Good Samaritan Prof. Bldg., Suite 201, 5601 Loch Raven Blvd., Baltimore, MD 21239
