Inhibitory Effects of 1',2'-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo.
10.11637/kjpa.2011.24.3.165
- Author:
Kwang Jin KIM
1
;
Han Bok KWAK
;
Eun Yong CHOI
;
Jaemin OH
;
Min Kyu CHOI
;
Jeong Hugh LEE
;
Mi Jin SONG
;
Yong Hwan AHN
;
Myeung Su LEE
;
Chang Hoon LEE
;
Seong Hoon PARK
;
Soo Uk CHAE
;
Myung Hee KIM
;
Seong Hwan KIM
;
Kie In PARK
;
Kwang Mee KIM
;
Ha Young KIM
;
Seo Young MOON
;
Jeong Joong KIM
Author Information
1. Department of Anatomy & Institute for Environmental Science, Korea. jjkim@wku.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Osteoclast;
RANKL;
1',2'-dihydrorotenone;
Resorption
- MeSH:
Bone Marrow;
Bone Resorption;
Humans;
Macrophages;
Osteoclasts;
Receptor Activator of Nuclear Factor-kappa B;
Rotenone
- From:Korean Journal of Physical Anthropology
2011;24(3):165-174
- CountryRepublic of Korea
- Language:English
-
Abstract:
It is important to identify therapeutic compounds with no adverse effects for use in the chemotherapy of patients with bone-related diseases. The aim of this study was to identify a new compound that inhibits osteoclast differentiation and bone resorption. Herein, we examined the effects of 1',2'-dihydrorotenone on osteoclast differentiation and bone resorption in vitro and in vivo. 1',2'-dihydrorotenone inhibited receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation of cultured bone marrow macrophages (BMMs) in a dose-dependent manner. However, 1',2'-dihydrorotenone did not exert cytotoxic effect on BMMs. 1',2'-dihydrorotenone suppressed the expression of c-fos and NFATc1 as well as osteoclast-specific genes in BMMs treated with RANKL. Treatment with RANKL inhibited the expression of inhibitors of differentiation/DNA binding (Id)1, 2, and 3; however, in the presence of 1',2'-dihydrorotenone, RANKL did not suppress the expression of Id1, 2, and 3. Furthermore, 1',2'-dihydrorotenone inhibited bone resorption and considerably attenuated the erosion of trabecular bone induced by lipopolysaccharide treatment. Taken together, these results suggest that 1',2'-dihydrorotenone has the potential to be applied in therapies for bone-related diseases.