Abstract

Omeprazole suppresses excessive secretion of gastric acid via irreversible inhibition of H⁺/K⁺-ATPase in the gastric parietal cells. Recent meta-analysis of data revealed an association between the use of proton pump inhibitors (PPIs) and increased risk of bone fractures, but the underlying molecular mechanism of PPI action remains unclear. In this study, we demonstrated that omeprazole directly influences bone metabolism using a unique in vitro bioassay system with teleost scales, as well as the in vivo model. The in vitro study showed that omeprazole significantly increased the activities of alkaline phosphatase and tartrate-resistant acid phosphatase after 6 h of incubation with this PPI. Expression of mRNAs for several osteoclastic markers was upregulated after 3-h incubation of fish scales with 10⁻⁷ M omeprazole. The in vivo experiments revealed that the plasma calcium levels significantly increased in the omeprazole-treated group. The results of in vitro and in vivo studies suggest that omeprazole affects bone cells by increasing bone resorption by upregulating expression of osteoclastic genes and promoting calcium release to the circulation. The suggested in vitro bioassay in fish scales is a practical model that can be used to study the effects of drugs on bone metabolism.

中文翻译：

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奥美拉唑对体内和体外鱼鳞模型中成骨细胞和破骨细胞的影响

摘要

奥美拉唑通过不可逆地抑制胃壁细胞中的 H ⁺ /K ⁺ -ATP 酶来抑制胃酸的过度分泌。最近对数据的荟萃分析揭示了质子泵抑制剂 (PPI) 的使用与骨折风险增加之间的关联，但 PPI 作用的潜在分子机制仍不清楚。在这项研究中，我们使用具有硬骨鱼鳞片的独特体外生物测定系统以及体内模型证明了奥美拉唑直接影响骨代谢。体外的研究表明，奥美拉唑与该 PPI 孵育 6 小时后，碱性磷酸酶和耐酒石酸酸性磷酸酶的活性显着增加。^{在用 10 -7} M 奥美拉唑孵育鱼鳞 3 小时后，几种破骨细胞标志物的 mRNA 表达上调。体内实验表明，奥美拉唑治疗组的血浆钙水平显着增加。体外和体内研究结果表明，奥美拉唑通过上调破骨细胞基因的表达和促进钙释放到循环中来增加骨吸收，从而影响骨细胞。建议的体外鱼鳞生物测定是一种实用的模型，可用于研究药物对骨代谢的影响。