Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Amorphigenin inhibits Osteoclast differentiation by suppressing c-Fos and nuclear factor of activated T cells

  • Kim, Bong-Gyu (Department of Orthopedic Surgery, School of Medicine, Wonkwang University) ;
  • Kwak, Han-Bok (Department of Anatomy, School of Medicine, Wonkwang University) ;
  • Choi, Eun-Yong (Department of Anatomy, School of Medicine, Wonkwang University) ;
  • Kim, Hun-Soo (Department of Pathology, School of Medicine, Wonkwang University) ;
  • Kim, Myung-Hee (Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology) ;
  • Kim, Seong-Hwan (Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology) ;
  • Choi, Min-Kyu (Department of Anatomy, School of Medicine, Wonkwang University) ;
  • Chun, Churl-Hong (Department of Orthopedic Surgery, School of Medicine, Wonkwang University) ;
  • Oh, Jae-Min (Department of Anatomy, School of Medicine, Wonkwang University) ;
  • Kim, Jeong-Joong (Department of Anatomy, School of Medicine, Wonkwang University)
  • Received : 2010.11.03
  • Accepted : 2010.12.08
  • Published : 2010.12.30
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Abstract

Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types. The main aim of this study was to investigate the effects of amorphigenin on osteoclast differentiation in vitro and on LPS treated inflammatory bone loss model in vivo. We show here that amorphigenin inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose dependent manner without cellular toxicity. Anti-osteoclastogenic properties of amorphigenin were based on a down-regulation of c-fos and NFATc1. Amorphigenin markedly inhibited RANKL-induced p38 and NF-${\kappa}$B pathways, but other pathways were not affected. Micro-CT analysis of the femurs showed that amorphigenin protected the LPS-induced bone loss. We concluded that amorphigenin can prevent inflammation-induced bone loss. Thus we expect that amorphigenin could be a treatment option for bone erosion caused by inflammation.

Keywords

Acknowledgement

Supported by : Wonkwang University

References

  1. Bartold PM, Marshall RI, Haynes DR. (2005). Periodontitis and rheumatoid arthritis: a review. J Periodontol 76(11 Suppl): 2066-2074 https://doi.org/10.1902/jop.2005.76.11-S.2066
  2. Bharti AC, Takada Y, Aggarwal BB. (2004). Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 172: 5940-5947 https://doi.org/10.4049/jimmunol.172.10.5940
  3. Body JJ. (2002). Calcitonin for the long-term prevention and treatment of postmenopausal osteoporosis. Bone 30(5 Suppl): 75S-79S https://doi.org/10.1016/S8756-3282(02)00715-9
  4. Boyle WJ, Simonet WS, Lacey DL. (2003). Osteoclast differentiation and activation. Nature 423: 337-342 https://doi.org/10.1038/nature01658
  5. Everts V, de Vries TJ, Helfrich MH. (2009). Osteoclast heterogeneity: lessons from osteopetrosis and inflammatory conditions. Biochim Biophys Acta 1792: 757-765 https://doi.org/10.1016/j.bbadis.2009.05.004
  6. Filleul O, Crompot E, Saussez S. (2010). Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 136: 1117-1124 https://doi.org/10.1007/s00432-010-0907-7
  7. Hayashi S, Yamane T, Miyamoto A, et al. (1998). Commitment and differentiation of stem cells to the osteoclast lineage. Biochem Cell Biol 76: 911-922 https://doi.org/10.1139/o98-099
  8. Hu JP, Nishishita K, Sakai E, et al. (2008). Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways. Eur J Pharmacol 580: 70-79 https://doi.org/10.1016/j.ejphar.2007.11.013
  9. Kim K, Lee SH, Ha Kim J, Choi Y, Kim N. (2008). NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol Endocrinol 22: 176-185 https://doi.org/10.1210/me.2007-0237
  10. Kloutek E, Popov A, Drenska D, Uzunov P. (1985). Experimental research on the hepatoprotective activity of flavonoids isolated from Amorpha fructiosa. Eksp Med Morfol 24: 50-54
  11. Kwak HB, Lee BK, Oh J, et al. (2010). Inhibition of osteoclast differentiation and bone resorption by rotenone, through down-regulation of RANKL-induced c-Fos and NFATc1 expression. Bone 46: 724-731 https://doi.org/10.1016/j.bone.2009.10.042
  12. Kwak HB, Yang D, Ha H, et al. (2006). Tanshinone IIA inhibits osteoclast differentiation through down-regulation of c-Fos and NFATc1. Exp Mol Med 38: 256-264 https://doi.org/10.1038/emm.2006.31
  13. Li YJ, Kim TH, Kwak HB, Lee ZH, Lee SY, Jhon GJ. (2007). Chloroform extract of deer antler inhibits osteoclast differentiation and bone resorption. J Ethnopharmacol 113: 191-198 https://doi.org/10.1016/j.jep.2007.04.020
  14. Lloyd M. (1998). Treatment of postmenopausal osteoporosis. N Engl J Med 339: 202 https://doi.org/10.1056/NEJM199807163390314
  15. Miyaura C, Inada M, Matsumoto C, et al. (2003). An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 197: 1303-1310 https://doi.org/10.1084/jem.20030015
  16. O'Regan RM, Gradishar WJ. (2001). Selective estrogen-receptor modulators in 2001. Oncology (Williston Park) 15: 1177-1185
  17. Park CK, Kim HJ, Kwak HB, et al. (2007). Inhibitory effects of Stewartia koreana on osteoclast differentiation and bone resorption. Int Immunopharmacol 7: 1507-1516 https://doi.org/10.1016/j.intimp.2007.07.016
  18. Rodan GA, Martin TJ. (2000). Therapeutic approaches to bone diseases. Science 289: 1508-1514 https://doi.org/10.1126/science.289.5484.1508
  19. Russell RG, Rogers MJ, Frith JC, et al. (1999). The pharmacology of bisphosphonates and new insights into their mechanisms of action. J Bone Miner Res 14(Suppl 2): 53-65 https://doi.org/10.1002/jbmr.5650140212
  20. Takayanagi H. (2005). Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med 83: 170-179 https://doi.org/10.1007/s00109-004-0612-6
  21. Takayanagi H. (2007). Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7: 292-304 https://doi.org/10.1038/nri2062
  22. Takayanagi H, Iizuka H, Juji T, et al. (2000). Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 43: 259-269 https://doi.org/10.1002/1529-0131(200002)43:2<259::AID-ANR4>3.0.CO;2-W
  23. Takayanagi H, Kim S, Koga T, et al. (2002). Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3: 889-901 https://doi.org/10.1016/S1534-5807(02)00369-6
  24. Teitelbaum SL. (2000). Bone resorption by osteoclasts. Science 289: 1504-1508 https://doi.org/10.1126/science.289.5484.1504
  25. Teitelbaum SL, Ross FP. (2003). Genetic regulation of osteoclast development and function. Nat Rev Genet 4: 638-649 https://doi.org/10.1038/nrg1122
  26. Walsh MC, Kim N, Kadono Y, et al. (2006). Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 24: 33-63 https://doi.org/10.1146/annurev.immunol.24.021605.090646
  27. Watts NB. (2003). Bisphosphonate treatment of osteoporosis. Clin Geriatr Med 19: 395-414 https://doi.org/10.1016/S0749-0690(02)00069-1
  28. Zhao Q, Shao J, Chen W, Li YP. (2007). Osteoclast differentiation and gene regulation. Front Biosci 12: 2519-2529 https://doi.org/10.2741/2252

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