Ho M L, Chang J K, Chuang L Y, Hsu H K, Wang G J
Department of Physiology, Kaohsiung Medical College, Taiwan, ROC.
Biochem Pharmacol. 1999 Sep 15;58(6):983-90. doi: 10.1016/s0006-2952(99)00186-0.
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.
据报道，非甾体抗炎药（NSAIDs）会抑制骨修复和骨重塑，但在修复过程的早期仅轻微抑制骨矿化。我们推测成骨细胞的增殖和/或分化早期可能受NSAIDs影响。本研究旨在调查NSAIDs是否影响成骨细胞的增殖和/或分化，以及这些作用是否由前列腺素（PG）介导。评估了前列腺素E1（PGE1）、前列腺素E2（PGE2）、吲哚美辛和酮咯酸对源自胎儿颅骨的富含成骨细胞培养物中胸苷掺入、细胞计数、细胞内碱性磷酸酶（ALP）活性和I型胶原含量的影响。结果表明，PGs和NSAIDs均以时间和浓度依赖性方式抑制DNA合成和细胞有丝分裂。然而，在成骨细胞分化的早期阶段，细胞内ALP活性和I型胶原含量受到刺激。这些结果表明：（i）酮咯酸对成骨细胞增殖的抑制作用有助于其对体内骨修复和重塑的抑制作用；（ii）PGEs和NSAIDs可能参与成骨细胞分化早期的基质成熟和生物性骨矿化；（iii）酮咯酸和吲哚美辛对细胞增殖和分化的作用可能不是通过抑制PGE1或PGE2的合成。
