The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effects of Achyranthis Bidentatae Radix on Osteoclast Differentiation and Bone Resorption

우슬의 파골세포 분화 억제와 골 흡수 억제효과

  • Kim, Ju-Ho (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University) ;
  • Ki, Ji-Ye (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University) ;
  • Ann, Ji-Young (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University) ;
  • Park, Hye-Jung (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University) ;
  • Kim, Hyun-Ju (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University) ;
  • Kwak, Han-Bok (Department of Anatomy, School of Medicine, and Wonkwang Medical Science Institute, Wonkwang University) ;
  • Oh, Jae-Min (Department of Anatomy, School of Medicine, and Wonkwang Medical Science Institute, Wonkwang University) ;
  • Kim, Yun-Kyung (Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University)
  • 김주호 (원광대학교 약학대학 한약학과.원광한약연구소) ;
  • 기지예 (원광대학교 약학대학 한약학과.원광한약연구소) ;
  • 안지영 (원광대학교 약학대학 한약학과.원광한약연구소) ;
  • 박혜정 (원광대학교 약학대학 한약학과.원광한약연구소) ;
  • 김현주 (원광대학교 약학대학 한약학과.원광한약연구소) ;
  • 곽한복 (원광대학교 의과대학 해부학교실.의과학연구소) ;
  • 오재민 (원광대학교 의과대학 해부학교실.의과학연구소) ;
  • 김윤경 (원광대학교 약학대학 한약학과.원광한약연구소)
  • Received : 2010.02.20
  • Accepted : 2010.03.22
  • Published : 2010.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Achyranthis Bidentatae Radix (ABR) has been used for treating of many symptoms especially osteoporosis and rheumatoid arthritis. In this study, we determined the effects of water extract of ABR in RANKL (Receptor Activator for Nuclear Factor $\kappa$ B Ligand)-induced osteoclast differentiation culture system. Methods : We assayed mRNA expression levels of NFATc1, c-Fos, TRAP, OSCAR, $FcR{\gamma}$, DAP12 and GAPDH in bone marrow macrophages (BMMs) treated with ABR. The protein expression levels of NFATc1, c-Fos, MAPKs and $\beta$-actin in cell lysates treated with ABR were analysed by Western blotting. In addition we determined the effects of water extract of ABR on LPS-induced bone-loss mouse. Results : Water extract of ABR showed remarkable inhibition on RANKL-treated osteoclast differentiation without cytotoxicity. ABR down-regulated the induction of c-Fos and NFATc1 by RANKL. ABR suppressed phosphorylation of JNK, p38 and I-${\kappa}B$. ABR rescued bone erosion by LPS induction in vivo study. Conclusions : These results demonstrate that ABR may be a useful remedy for curing of bone-loss disease such as osteoporosis.

Keywords

References

  1. National Osteoporosis Foundation. America's Bone Health. The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC : National Osteoporosis Foundation. 2002.
  2. Reginster JY, Burlet N. Osteoporosis : a still increasing prevalence. Bone. 2006 ; 38 : S4-S9.
  3. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007 ; 22 : 465-75. https://doi.org/10.1359/jbmr.061113
  4. Alliston T, Derynck R. Interfering with bone remodelling. Nature. 2002 ; 416 : 686-7. https://doi.org/10.1038/416686a
  5. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003 ; 423 : 337-42. https://doi.org/10.1038/nature01658
  6. Darnay BG, Ni J, Moore PA, Aggarwal BB. Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaBinducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem. 1999 ; 274 : 7724-31. https://doi.org/10.1074/jbc.274.12.7724
  7. Lee ZH, Kim HH. Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun. 2003 ; 305 : 211-4. https://doi.org/10.1016/S0006-291X(03)00695-8
  8. Chesnut CH III, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004 ; 19 : 1241-9. https://doi.org/10.1359/JBMR.040325
  9. Ringe JD, Dorst A, Faber H, Ibach K, Sorenson F. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroidinduced osteoporosis : results from a long-term comparative study. Osteoporos Int. 2003 ; 14 : 801-7. https://doi.org/10.1007/s00198-003-1425-0
  10. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators JAMA. 1999 ; 282 : 637-45. https://doi.org/10.1001/jama.282.7.637
  11. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 ; 344 : 1434-41. https://doi.org/10.1056/NEJM200105103441904
  12. Kwak HB, Kim JH, Kim DJ, Kwon YM, Oh JM, Kim YK. Effect of Water Extract of Deer Antler in Osteoclast Differentiation. Korean J Oriental Physiology & Pathology. 2008 ; 22(4) : 891-5.
  13. Park CK, Kim HJ, Kwak HB, Lee TH, Bang MH, Kim CM, Lee Y, Chung DK, Baek NI, Kim J, Lee ZH, Kim HH. Inhibitory effects of Stewartia koreana on osteoclast differentiation and bone resorption. International Immunopharmacology. 2007 ; 7 : 1507-16. https://doi.org/10.1016/j.intimp.2007.07.016
  14. Han KY, Yang D, Chang EJ, Lee Y, Hao Huang, Sung SH, Lee ZH, Kim YC, Kim HH. Inhibition of osteoclast differentiation and bone resorption by sauchinone. Biochemical Pharmacology. 2007 ; 74 : 911-23. https://doi.org/10.1016/j.bcp.2007.06.044
  15. Tsai HY, Lin HY, Fong YC, Wu JB, Chen YF, Tsuzuki, Tang CH. Paeonol inhibits RANKLinduced osteoclastogenesis by inhibiting ERK, p38 and $NF_kB$ pathway. European Journal of Pharmacology. 2008 ; 588 : 124-33. https://doi.org/10.1016/j.ejphar.2008.04.024
  16. Juan Li, Hui Qi, Lian-Wen Qi, Ling Yi, Ping Li. Simultaneous determination of main phytoecdysones and triterpenoids in Radix Achyranthis Bidentatae by high-performance liquid chromatography with diode array-evaporative light scattering detectors and mass spectrometry. Analytica Chimica Acta. 2007 ; 596 : 264-72. https://doi.org/10.1016/j.aca.2007.05.016
  17. Lu T, Mao C, Zhang L, Xu W. The research on analgestic and anti-inflammatory action of different processed products of Achyranthes bidentata. Zhong Yao Cai. 1997 ; 20(10) : 507-9.
  18. Chen XM, Tian GY. Structural elucidation and antitumor activity of a fructan from Cyathula officinalis Kuan. Carbohydr Res. 2003 ; 338(11) : 1235-41. https://doi.org/10.1016/S0008-6215(03)00073-9
  19. Gao XY, Wang DW, Li FM. Determination of ecdysterone in Achyranthes Bidentata Bl and its activity promoting proliferation of osteoblast-like cells. Yao Xue Xue Bao. 2000 ; 35(11) : 868-70.
  20. Rodan GA, Raisz LG, Bilezikian JP. Principles of bone biology. Pathophysiology of osteoporosis. 2002 ; 1275-89.
  21. Yavropoulou MP, Yovos JG. Osteoclstogenesis Current knowledge and future perspectives. J Musculoskelet Neuronal Interact. 2008 ; 8(3) : 204-16.
  22. Dai XM. Targeted disruption of the mouse colonystimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002 ; 99 : 111-28. https://doi.org/10.1182/blood.V99.1.111
  23. Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S. Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med. 2002 ; 347 : 175-84. https://doi.org/10.1056/NEJMoa013096
  24. Kobayashi T, Walsh PT, Walsh MC, Speirs KM, Chiffoleau E, King CG, Hancock WW, Caamano JH, Hunter CA, Scott P, Turka LA, Choi Y. TRAF6 is a critical factor for dendritic cell maturation and development. Immunity. 2003 ; 19 : 353-63. https://doi.org/10.1016/S1074-7613(03)00230-9
  25. Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking $NF_kB1$ and $NF_kB2$. Nat Med. 1997 ; 3 : 1285-9. https://doi.org/10.1038/nm1197-1285
  26. Komarova SV, Pilkington MF, Weidema AF, Dixon SJ, Sims SM. RANK ligand-induced elevation of cytosolic $Ca^{2+}$ accelerates nuclear translocation of $NF_kB$ in osteoclasts. J Biol Chem. 2003 ; 278 : 8286-93. https://doi.org/10.1074/jbc.M206421200
  27. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E. Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 1999 ; 96 : 3540-5. https://doi.org/10.1073/pnas.96.7.3540
  28. Lee SE, Chung WJ, Kwak HB, Chung CH, Kwack KB, Lee ZH. Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem. 2001 ; 276 : 49343-9. https://doi.org/10.1074/jbc.M103642200
  29. Lee SE, Woo KM, Kim SY, Kim HM, Kwack K, Lee ZH. The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone. 2002 ; 30 : 71-7.
  30. Li X, Udagawa N, Itoh K, Suda K, Murase Y, Nishihara T. p38 MAPK-mediated signals are required for inducing osteoclast differentiation but not for osteoclast function. Endocrinology. 2002 ; 143 : 3105-13. https://doi.org/10.1210/en.143.8.3105
  31. Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M. Involvement of p38 mitogenactivated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of $NF-\kappa B$ ligand (RANKL). J Biol Chem. 2000 ; 275 : 31155-61. https://doi.org/10.1074/jbc.M001229200
  32. Kwak HB, Lee SW, Li YJ, Kim YA, Han SY, Jhon GJ, Kim HH, Lee ZH. Inhibitory of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative, SCOH. Biochemical Pharmacology. 2004 ; 67 : 1239-48. https://doi.org/10.1016/j.bcp.2003.10.032
  33. Basu S, Kolesnick R. Stress signals for apoptosis: ceramide and c-Jun kinase. Oncogene. 1998 ; 17 : 3277-85. https://doi.org/10.1038/sj.onc.1202570
  34. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002 ; 3 : 889-901. https://doi.org/10.1016/S1534-5807(02)00369-6
  35. Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer. 2003 ; 3 : 859-68. https://doi.org/10.1038/nrc1209
  36. Wagner EF, Eferl R. Fos/AP-1 proteins in bone and the immune system. Immunol Rev. 2005 ; 208 : 126-40. https://doi.org/10.1111/j.0105-2896.2005.00332.x
  37. Wang ZQ, Ovitt C, Grigoriadis AE, Mohle-Steinlein U, Ruther U, Wagner EF. Bone and haematopoietic defects in mice lacking c-fos. Nature. 1992 ; 360 : 741-5. https://doi.org/10.1038/360741a0
  38. Hiroshi Takayanagi. Amazing multifunctionality of calcineurin and NFAT signaling in bone homeostasis. BoneKEy-Osteovision. 2006 ; 3 : 28-31. https://doi.org/10.1138/20060231
  39. Matsumoto M, Kogawa M, Wada S, Takayanagi H, Tsujimoto M, Katayama S, Hisatake K, Nogi Y. Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J Biol Chem. 2004 ; 279 : 45969-79. https://doi.org/10.1074/jbc.M408795200
  40. Kim Y, Sato K, Asagiri M, Morita I, Soma K, Takayanagi H. Contribution of NFATc1 to the transcriptional control of immunoreceptor OSCAR but not TREM-2 during osteoclastogenesis. J Biol Chem. 2005 ; 280 : 32905-13. https://doi.org/10.1074/jbc.M505820200
  41. Mocsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC. The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci USA. 2004 ; 101 : 6158-63. https://doi.org/10.1073/pnas.0401602101
  42. Suda K, Woo JT, Takami M, Sexton PM, Nagai K. Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-alpha, IL-1, and RANKL. J Cell Physiol. 2002 ; 190 : 101-8. https://doi.org/10.1002/jcp.10041
  43. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000 ; 406 : 782-7. https://doi.org/10.1038/35021228

Cited by

  1. 하이드로젤에 탑재한 우슬(牛膝)추출물의 효과적인 파골세포 분화 억제 작용 vol.25, pp.1, 2010, https://doi.org/10.15204/jkobgy.2012.25.1.001
  2. 천연자(川楝子)의 파골세포 분화 억제기전 연구 vol.25, pp.2, 2010, https://doi.org/10.15204/jkobgy.2012.25.2.001
  3. 호장근(虎杖根)의 파골세포 분화 억제 효과와 기전 연구 vol.27, pp.1, 2010, https://doi.org/10.15204/jkobgy2014.27.1.017
  4. 영지(靈芝) 추출물이 Rat fetus 두개골로부터 분리한 조골세포에 미치는 영향 vol.27, pp.2, 2010, https://doi.org/10.15204/jkobgy.2014.27.2.023
  5. 하고초(夏枯草)에서 추출한 Ursolic acid의 파골세포 분화 억제 효과 vol.27, pp.2, 2010, https://doi.org/10.15204/jkobgy.2014.27.2.059