Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species.
10.3858/emm.2011.43.11.067
- Author:
Ho Jin MOON
1
;
Sung Eun KIM
;
Young Pil YUN
;
Yu Shik HWANG
;
Jae Beum BANG
;
Jae Hong PARK
;
Il Keun KWON
Author Information
1. Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea. kwoni@khu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
bone resorption;
mitogen-activated protein kinases;
osteoclast;
RANK ligand;
reactive oxygen species;
simvastatin
- MeSH:
Acid Phosphatase/genetics/metabolism;
Animals;
Anticholesteremic Agents/*pharmacology;
Blotting, Western;
*Cell Differentiation;
Cells, Cultured;
Hydrogen Peroxide/pharmacology;
Isoenzymes/genetics/metabolism;
Macrophages/cytology/drug effects/metabolism;
Mice;
Mitogen-Activated Protein Kinases/genetics/metabolism;
NF-kappa B/genetics/metabolism;
Osteoclasts/*cytology/*drug effects/metabolism;
RANK Ligand/metabolism;
RNA, Messenger/genetics;
Reactive Oxygen Species/*metabolism;
Real-Time Polymerase Chain Reaction;
Simvastatin/*pharmacology
- From:Experimental & Molecular Medicine
2011;43(11):605-612
- CountryRepublic of Korea
- Language:English
-
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.
