TY - JOUR
T1 - Nitric oxide induces osteoblast apoptosis through a mitochondria-dependent pathway
AU - Ho, Wei-Pin
AU - Chen, Ta-Liang
AU - Chiu, Wen-Ta
AU - Tai, Yu-Ting
AU - Chen, Ruei-Ming
PY - 2005
Y1 - 2005
N2 - Osteoblasts contribute to bone remodeling. Nitric oxide can regulate osteoblast activities. In this study, we attempted to evaluate the pathophysiological effects of nitric oxide on osteoblasts and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside, a nitric oxide donor, decreased alkaline phosphatase activities and cell viability in a concentration- and time-dependent manner. Apoptotic analysis revealed that sodium nitroprusside time-dependently increased the percentages of osteoblasts undergoing apoptosis. Administration of sodium nitroprusside reduced the mitochondrial membrane potential of osteoblasts. In parallel with the mitochondrial dysfunction, levels of intracellular reactive oxygen species and cytochrome c were significantly elevated following sodium nitroprusside administration. Exposure of osteoblasts to sodium nitroprusside significantly increased caspase-3 activity. Results of this study show that nitric oxide, decomposed from sodium nitroprusside, can induce osteoblast apoptosis through a mitochondrion-dependent cascade that causes mitochondrial dysfunction, release of intracellular reactive oxygen species and cytochrome c from mitochondria to cytoplasm, and activation of caspase-3.
AB - Osteoblasts contribute to bone remodeling. Nitric oxide can regulate osteoblast activities. In this study, we attempted to evaluate the pathophysiological effects of nitric oxide on osteoblasts and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside, a nitric oxide donor, decreased alkaline phosphatase activities and cell viability in a concentration- and time-dependent manner. Apoptotic analysis revealed that sodium nitroprusside time-dependently increased the percentages of osteoblasts undergoing apoptosis. Administration of sodium nitroprusside reduced the mitochondrial membrane potential of osteoblasts. In parallel with the mitochondrial dysfunction, levels of intracellular reactive oxygen species and cytochrome c were significantly elevated following sodium nitroprusside administration. Exposure of osteoblasts to sodium nitroprusside significantly increased caspase-3 activity. Results of this study show that nitric oxide, decomposed from sodium nitroprusside, can induce osteoblast apoptosis through a mitochondrion-dependent cascade that causes mitochondrial dysfunction, release of intracellular reactive oxygen species and cytochrome c from mitochondria to cytoplasm, and activation of caspase-3.
KW - Apoptosis
KW - Caspase-3
KW - Mitochondrial functions
KW - Nitric oxide
KW - Osteoblasts
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U2 - 10.1196/annals.1338.039
DO - 10.1196/annals.1338.039
M3 - Article
C2 - 15965092
AN - SCOPUS:22044438721
SN - 0077-8923
VL - 1042
SP - 460
EP - 470
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -