Molecular mechanism of nitric oxide-induced osteoblast apoptosis

Ruei-Ming Chen, Ta-Liang Chen, Wen-Ta Chiu, Chia Chen Chang

研究成果: 雜誌貢獻文章

62 引文 (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

指紋

Nitroprusside
Osteoblasts
Nitric Oxide
Apoptosis
Mitochondrial Membrane Potential
Lipopolysaccharides
Reactive Oxygen Species
Cell Survival
Adenosine Triphosphate
Electron Transport Complex I
bcl-2-Associated X Protein
Proteins
Nitric Oxide Donors
DNA Fragmentation
Nitrites
L-Lactate Dehydrogenase
Immunoblotting
NAD
Culture Media
Oxidative Stress

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

引用此文

Molecular mechanism of nitric oxide-induced osteoblast apoptosis. / Chen, Ruei-Ming; Chen, Ta-Liang; Chiu, Wen-Ta; Chang, Chia Chen.

於: Journal of Orthopaedic Research, 卷 23, 編號 2, 03.2005, p. 462-468.

研究成果: 雜誌貢獻文章

@article{d5d65810586742dc82c86e0e2fc05b94,
title = "Molecular mechanism of nitric oxide-induced osteoblast apoptosis",
abstract = "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.",
keywords = "Apoptosis, Bcl-2 protein, Mitochondrial functions, Nitric oxide, Osteoblasts, Reactive oxygen species",
author = "Ruei-Ming Chen and Ta-Liang Chen and Wen-Ta Chiu and Chang, {Chia Chen}",
year = "2005",
month = "3",
doi = "10.1016/j.orthres.2004.08.011",
language = "English",
volume = "23",
pages = "462--468",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Molecular mechanism of nitric oxide-induced osteoblast apoptosis

AU - Chen, Ruei-Ming

AU - Chen, Ta-Liang

AU - Chiu, Wen-Ta

AU - Chang, Chia Chen

PY - 2005/3

Y1 - 2005/3

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bcl-2 protein

KW - Mitochondrial functions

KW - Nitric oxide

KW - Osteoblasts

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=14244250783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14244250783&partnerID=8YFLogxK

U2 - 10.1016/j.orthres.2004.08.011

DO - 10.1016/j.orthres.2004.08.011

M3 - Article

C2 - 15734263

AN - SCOPUS:14244250783

VL - 23

SP - 462

EP - 468

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 2

ER -