Inhibitory Effects of 1′,2′-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo

Kwang-Jin Kim (김광진); 곽한복; 최은영; 오재민; 최민규; 이정휴; 송미진; 안용환; 이명수; Chang Hoon Lee (이창훈); 박성훈; 김명희; 김성환; 박기인; 김광미; 김하영; 문서영; 김정중; 채수욱

doi:10.11637/aba.2011.24.3.165

Inhibitory Effects of 1′,2′-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo

Anatomy & Biological Anthropology
Abbr : Anat Biol Anthropol
2011, 24(3), pp.165~174
DOI : 10.11637/aba.2011.24.3.165
Publisher : 대한체질인류학회
Research Area : Medicine and Pharmacy > Anatomy

Kwang-Jin Kim ¹, 곽한복 ², 최은영 ², 오재민 ², 최민규 ², 이정휴 ², 송미진 ², 안용환 ², 이명수 ², Chang Hoon Lee ², 박성훈 ², 김명희 ³, 김성환 ³, 박기인 ⁴, 김광미 ⁵, 김하영 ², 문서영 ², 김정중 ², 채수욱 ²

¹원광대학교
²원광대학교
³대전 화학연구원
⁴전북대학교
⁵초당대학교

Accredited

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-κB ligand (RANKL)-induced osteoclast differentiation of cultured bone marrow macrophages (BMMs) in a dosedependent 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.

KEYWORDS

Osteoclast, RANKL, 1′, 2′-dihydrorotenone, Resorption

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[journal] Benezra R / 1990 / The protein Id: a negative regulator of helix-loop-helix DNA binding proteins / Cell 61 : 49~59

[journal] Boyle WJ / 2003 / Osteoclast differentiation and activation / Nature 423 : 337~342

[journal] Kim K / 2005 / Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation- induced cytokine-mediated osteoclastogenesis / J Biol Chem 280 : 35209~35216

[journal] Kim K / 2007 / MafB negatively regulates RANKL-mediated osteoclast differentiation / BLOOD / AMER SOC HEMATOLOGY 109(8) : 3253~3259

[journal] Kim MH / 2009 / Saurolactam Inhibits Osteoclast Differentiation and Stimulates Apoptosis of Mature Osteoclasts / JOURNAL OF CELLULAR PHYSIOLOGY / WILEY-LISS 221 : 618~628

[journal] Kim N / 2000 / Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene / Proc Natl Acad Sci USA 97 : 10905~10910

[journal] Kobayashi K / 2000 / Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction / J Exp Med 191 : 275~281

[journal] Kong YY / 1999 / OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis / Nature 397 : 315~323

[journal] Kwak HB / 2010 / Inhibition of osteoclast differentiation and bone resorption by rotenone, through down-regulation of RANKL-induced c-Fos and NFATc1 expression / BONE / ELSEVIER SCIENCE INC 46 : 724~731

[journal] Kwak HB / 2008 / Tanshinone IIA suppresses inflammatory bone loss by inhibiting the synthesis of prostaglandin E2 in osteoblasts / European Journal of Pharmacology / Elsevier BV 601(1-3) : 30~37

[journal] Lee J / 2006 / d helixloop- helix proteins negatively regulate TRANCEmediated osteoclast differentiation / Blood 107 : 2686~2693

[journal] Massari ME / 2000 / Helix-loop-helix proteins: regulators of transcription in eukaryotic organisms / Mol Cell Biol 20 : 429~440

[journal] Matsuo K / 2000 / Fosl1 is a transcription target of c-Fos during osteoclast differentiation / Nat Genet 24 : 184~187

[journal] Miyaura C / 2003 / An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated boneresorption associated with inflammation / J Exp Med 197 : 1303~1310

[journal] Otero JE / 2010 / IKKbeta activation is sufficient for RANK-independent osteoclast differentiation and osteolysis / J Bone Miner Res 25 : 1282~1294

[journal] Putnam SE / 2007 / Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health / Phytother Res 21 : 99~112

[journal] Rodan GA / 2000 / herapeutic approaches to bone diseases / Science 289 : 1508~1514

[journal] Suda T / 1999 / Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families / Endocr Rev 20 : 345~357

[journal] Takayanagi H / 2007 / Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems / Nat Rev Immunol 7 : 292~304

[journal] Takayanagi H / 2002 / Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts / Dev Cell 3 : 889~901

[journal] Takayanagi H / 2000 / T-cell-mediated regulation of osteoclastogenesis by signaling cross-talk between RANKL and IFN-gamma / Nature 408 : 600~605

[journal] Tanabe N / 2005 / Il-1 alpha stimulates the formation of osteoclast- like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts / Life Sci 77 : 615~626

[journal] Teitelbaum SL / 2003 / Bone resorption by osteoclasts / Science 289 : 1504~1508

[journal] Walsh MC / 2003 / Biology of the TRANCE axis / Cytokine Growth Factor Rev 14 : 251~263

[journal] Walsh MC / 2006 / Osteoimmunology: Interplay between the immune system and bone metabolism / ANNUAL REVIEW OF IMMUNOLOGY / ANNUAL REVIEWS 24 : 33~63

[journal] Wong BR / 1998 / The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor / J Biol Chem 273 : 28355~28359

[journal] Yamashita T / 2007 / NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1 / J Biol Chem 282 : 18245~18253

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Inhibitory Effects of 1′,2′-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo

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Anatomy & Biological Anthropology 2025 KCI Impact Factor : 0.29

Inhibitory Effects of 1′,2′-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo

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