Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species
Experimental & Molecular Medicine
; : 605-612, 2011.
Article
в En
| WPRIM
| ID: wpr-122149
Ответственная библиотека:
WPRO
ABSTRACT
Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-kappaB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.
Key words
Полный текст:
1
База данных:
WPRIM
Основная тема:
Osteoclasts
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Acid Phosphatase
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RNA, Messenger
/
Cell Differentiation
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Cells, Cultured
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Blotting, Western
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NF-kappa B
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Reactive Oxygen Species
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Simvastatin
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Mitogen-Activated Protein Kinases
Пределы темы:
Animals
Язык:
En
Журнал:
Experimental & Molecular Medicine
Год:
2011
Тип:
Article