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Effects of nonsteroidal anti-inflammatory drugs and prostaglandins on osteoblastic functions
M L Ho1, J K Chang, L Y Chuang
1Department of Physiology, Kaohsiung Medical College, Taiwan, ROC. m675005@cc.kmc.edu.tw
Abstract:
It has been reported that nonsteroidal anti-inflammatory drugs (NSAIDs) suppress bone repair and bone remodeling but only mildly inhibit bone mineralization at the earlier stage of the repair process. We proposed that the proliferation and/or the earlier stage of differentiation of osteoblasts may be affected by NSAIDs. This study was designed to investigate whether NSAIDs affect the proliferation and/or differentiation of osteoblasts and whether these effects are prostaglandin (PG) mediated. The effects of PGE1 and PGE2, indomethacin, and ketorolac on thymidine incorporation, cell count, intracellular alkaline phosphatase (ALP) activity, and Type I collagen content in osteoblast-enriched cultures derived from fetal calvaria were evaluated. The results showed that both PGs and NSAIDs inhibited DNA synthesis and cell mitosis in a time- and concentration-dependent manner. However, intracellular ALP activity and Type I collagen content were stimulated at an earlier stage of differentiation in osteoblasts. These results suggested that (i) the inhibitory effect of ketorolac on osteoblastic proliferation contributes to its suppressive effects on bone repair and remodeling in vivo; (ii) PGEs and NSAIDs may be involved in matrix maturation and biologic bone mineralization in the earlier stage of osteoblast differentiation; and (iii) the effects of ketorolac and indomethacin on cell proliferation and differentiation may not be through the inhibition of the synthesis of PGE1 or PGE2.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostaglandins (PGs) inhibit osteoblast proliferation but stimulate early differentiation markers. NSAID effects on bone repair may involve proliferation inhibition, not solely PG synthesis reduction.
Area of Science:
- Bone Biology and Pharmacology
- Osteoblast Differentiation and Prostaglandin Signaling
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to impair bone repair and remodeling.
- Previous research suggests NSAIDs mildly inhibit early bone mineralization, prompting investigation into their effects on osteoblast proliferation and differentiation.
Purpose of the Study:
- To investigate the impact of NSAIDs on osteoblast proliferation and differentiation.
- To determine if these effects are mediated by prostaglandin (PG) pathways.
Main Methods:
- Evaluated the effects of PGE1, PGE2, indomethacin, and ketorolac on osteoblast-enriched cultures from fetal calvaria.
- Assessed thymidine incorporation, cell count, intracellular alkaline phosphatase (ALP) activity, and Type I collagen content.
Main Results:
- Both PGs and NSAIDs demonstrated time- and concentration-dependent inhibition of DNA synthesis and cell mitosis.
- Intracellular ALP activity and Type I collagen content were stimulated during the earlier stages of osteoblast differentiation.
- Ketorolac and indomethacin's effects on proliferation and differentiation may not be solely due to reduced PGE1 or PGE2 synthesis.
Conclusions:
- Ketorolac's inhibition of osteoblastic proliferation contributes to its suppressive effects on bone repair and remodeling.
- Prostaglandins and NSAIDs appear to influence matrix maturation and early biologic bone mineralization in osteoblasts.
- The mechanism of action for ketorolac and indomethacin on osteoblasts may involve pathways independent of prostaglandin synthesis inhibition.