Korean J Phys Anthropol.
2011 Sep;24(3):165-174.
Inhibitory Effects of 1',2'-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo
- Affiliations
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- 1Department of Anatomy & Institute for Environmental Science, Korea. jjkim@wku.ac.kr
- 2Department of Internal Medicine, Division Rheumatology & Institute of Wonkwang Medical Science, Korea.
- 3Department of Radiology, Wonkwang University School of Medicine, Korea.
- 4Department of Orthopedic Surgery, Wonkwang University School of Medicine, Korea.
- 5Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon, Korea.
- 6Division of Biological Science, School of Natural Science, Chonbuk National University, Korea.
- 7Department of Nursing, Chodang University, Muan, Korea.
- 8Department of Internal Medicine, Division of Endocrinology and Metabolism, Korea.
- 9Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Sanbon Medical Center, Korea.
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.
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