Molecular mechanism of nitric oxide-induced osteoblast apoptosis

研究成果: 雜誌貢獻文章

62 引文 斯高帕斯(Scopus)

摘要

Nitric oxide (NO) can regulate osteoblast activities. Our previous study showed that NO induced osteoblast apoptosis [Chen RM, Liu HC, Lin YL, Jean WC, Chen JS, Wang JH. Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein. J Orthop Res 2002;20:295-302]. This study was further aimed to evaluate the mechanism of NO-induced osteoblast apoptosis from the viewpoints of mitochondrial functions, intracellular oxidative stress, and the anti-apoptotic Bcl-2 protein using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP), an NO donor, significantly increased amounts of lactate dehydrogenase in the culture medium, and decreased cell viability in concentration- and time-dependent manners. Administration of SNP in osteoblasts time-dependently led to DNA fragmentation. The mitochondrial membrane potential was significantly reduced following SNP administration. SNP decreased complex I NADH dehydrogenase activity in a time-dependent manner. Levels of cellular adenosine triphosphate (ATP) were suppressed by SNP. In parallel with the mitochondrial dysfunction, SNP time-dependently increased levels of intracellular reactive oxygen species. Immunoblotting analysis revealed that SNP reduced Bcl-2 protein levels. Exposure to lipopolysaccharide (LPS) and IFN-γ significant increased endogenous nitrite production. In parallel with the increase in endogenous NO, administration of LPS and IFN-γ suppressed cell viability, mitochondrial membrane potential, and ATP synthesis. Results of this study show that NO released from SNP can induce osteoblast insults and apoptosis, and the mechanism may involve the modulation of mitochondrial functions, intracellular reactive oxygen species, and Bcl-2 protein.

原文英語
頁(從 - 到)462-468
頁數7
期刊Journal of Orthopaedic Research
23
發行號2
DOIs
出版狀態已發佈 - 三月 2005

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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