Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Inhibitory Effects of 1`,2`-Dihydrorotenone On Osteoclast Differentiation and Bone Resorption.
Lee1, Chang-Hoon, Sung2, Myung-Soon, Lee2, Eun-Gyeong, Hong2, Myong Joo, Yoo2, Wan-Hee
Department of Internal Medicine, School of medicine, Wonkwang university, Iksan, Chonbuk, South Korea
Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea
Osteoclasts, which are bone-resorbing multinucleated cells, are derived from hematopoietic cells of the monocyte-macrophage lineage and play a key role in bone resortion. Regulation of osteoclast fusion is important to treat of bone resorbing disease such as osteoporosis and rheumatoid arthritis. The aim of this study was to identify a new compound that inhibits osteoclast differentiation and bone resorption.
Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of 1`,2`-dihydrorotenone. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the MAPKs and NF-kB pathways were measured using Western blot analysis. Osteoclast function was evaluated with resorption pit assay. With LPS treated mouse model, We evaluated the effects of 1`,2`-dihydrorotenone on LPS induced bone loss when co-treated with it by using micro CT and histomorphometric analysis.
1`,2`-dihydrorotenone inhibited receptor activator of NF-kB 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.
To cite this abstract, please use the following information:
Lee, Chang-Hoon, Sung, Myung-Soon, Lee, Eun-Gyeong, Hong, Myong Joo, Yoo, Wan-Hee; Inhibitory Effects of 1`,2`-Dihydrorotenone On Osteoclast Differentiation and Bone Resorption. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1111