Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

Effect of Water Extract of Cynanchi Wilfordii Radix in RANKL-induced Osteoclast Differentiation

백하수오(白何首烏) 물 추출물의 파골세포 분화에 미치는 영향

  • Ahn, Yong-Hwan (Department of Anatomy, Institute for Skeletal Disease & Institute for Environmental Science, Wonkwang Medical Science, College of Medicine) ;
  • Oh, Jae-Min (Department of Anatomy, Institute for Skeletal Disease & Institute for Environmental Science, Wonkwang Medical Science, College of Medicine) ;
  • Lee, Myeung-Su (Department of Internal Medicine, Division of Rheumatology & Institute of Wonkwang Medical Science, College of Medicine) ;
  • Jung, Jong-Hyuk (Department of Internal Medicine, Division of Rheumatology & Institute of Wonkwang Medical Science, College of Medicine) ;
  • Chae, Soo-Uk (Department of Orthopedic Surgery, Gunsan Medical Center) ;
  • Moon, Seo-Young (Division of Anesthesiology and Pain Medicine, Sanbon Medical Center) ;
  • Jeon, Byung-Hoon (Department of Pathology & Research Center of Traditional Korean Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Choi, Min-Kyu (Department of Anatomy, Institute for Skeletal Disease & Institute for Environmental Science, Wonkwang Medical Science, College of Medicine)
  • 안용환 (원광대학교 의과대학 해부학교실, 골격계질환연구소 및 환경과학연구소) ;
  • 오재민 (원광대학교 의과대학 해부학교실, 골격계질환연구소 및 환경과학연구소) ;
  • 이명수 (원광대학교 의과대학 류마티스내과학교실 및 원광의과학연구소) ;
  • 정종혁 (원광대학교 의과대학 류마티스내과학교실 및 원광의과학연구소) ;
  • 채수욱 (군산병원 정형외과) ;
  • 문서영 (산본병원 마취통증의학과) ;
  • 전병훈 (한의과대학 병리학교실 및 한국전통의학연구소) ;
  • 최민규 (원광대학교 의과대학 해부학교실, 골격계질환연구소 및 환경과학연구소)
  • Received : 2012.02.06
  • Accepted : 2012.03.19
  • Published : 2012.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

Osteoporotic fracture became a serious social problem, which related with mortality and morbidity in old age population. Osteoclast which is responsible for bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Cynanchum wilfordii (Asclepiadaceae) roots have been used in Korean folk medicine for the treatment of diabetes mellitus and aging progression. Also, recent studies have shown that the extract and fractions of Cynanchi Wilfordii Radix have various pharmacological actions including scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the effect of extract of Cynanchi Wilfordii Radix in osteoclast differentiation had not been reported. Thus, we evaluated the effect of Cynanchi Wilfordii Radix on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Through our study, we found that Cynanchi Wilfordii Radix significantly inhibited osteoclast differentiation induced by RANKL. Cynanchi Wilfordii Radix suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Cynanchi Wilfordii Radix significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Cynanchi Wilfordii Radix inhibited the protein expression of c-fos and NFATc1. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

Keywords

References

  1. Cummings, S.R., Browner, W.S., Bauer, D., Stone, K., Ensrud, K., Jamal, S., Ettinger, B: Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. N Engl J Med 339: 733-738, 1998. https://doi.org/10.1056/NEJM199809103391104
  2. Looker, A., Johnston, C., Wahner, H., Dunn, W., Calvo, M., Harris, T., Heyse, S., Lindsay, R.J. Prevalence of low femoral bone density in older U.S. women from NHANES III. Bone Miner. Res. 10: 796-802, 1995.
  3. Park, C., Ha, Y.C., Jang, S., Jang, S., Yoon, H.K., Lee, Y.K. The incidence and residual lifetime risk of osteoporosis-related fractures in Korea. J Bone Miner Metab. Nov 29(6):744-751, 2011. https://doi.org/10.1007/s00774-011-0279-3
  4. Nishikawa, M., Akatsu, T., Katayama, Y., Yasutomo, Y., Kado, S., Kugal, N., Yamamoto, M., Nagata, N. Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone 18: 9-14, 1996. https://doi.org/10.1016/8756-3282(95)00426-2
  5. Khosla, S., Burr, D., Cauley, J., et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22: 1479-1491, 2007 https://doi.org/10.1359/jbmr.0707onj
  6. Park-Wyllie, L.Y., Mamdan,i M.M., Juurlink, D.N., Hawker, G.A., Gunraj, N., Austin, P.C., Whelan, D.B., Weiler, P.J., Laupacis, A. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. Feb 23; 305(8):783-789, 2011. https://doi.org/10.1001/jama.2011.190
  7. 정연태, 최윤홍, 송정훈, 이창훈, 오재민: 두충의 물 추출물이 파골세포의 분화에 미치는 영향. 동의생리병리학회지 23(3):613-618, 2009.
  8. 오재민, 이명수, 김정중, 이정휴, 채수욱, 김하영, 전병훈, 박기인, 문서영, 조해중: 파골세포 분화에 미치는 복분자 물 추출물의 효과. 동의생리병리학회지 25(4):669-674, 2011.
  9. 한기선, 신길조, 이원철, 이종형. 白何首烏항산화활성과 amino acid의 분포에 관한 실험적 연구. 대한 한방 내과학회지 19(2):411-430, 1998.
  10. Shan, L., Liu, R.H., Shen, Y.H., Zhang, W.D., Zhang, C., Wu, D.Z., Min, L., Su, J., Xu, X.K. Gastroprotective effect of a traditional Chinese herbal drug "Baishouwu" on experimental gastric lesions in rats. J. Ethnopharmacol. 107: 389-394, 2006. https://doi.org/10.1016/j.jep.2006.03.022
  11. Kim, M.S., Baek, J.H., Park, J.A., Hwang, B.Y., Kim, S.E., Lee, J.J., Kim, K.W. Wilfoside K1N isolated from Cynanchum wilfordii inhibits angiogenesis and tumor cell invasion. Int J Oncol. Jun;26(6):1533-1539, 2005.
  12. Korczowska, I., Olewicz-Gawlik, A. Does low-dose and short-term glucocorticoids treatment increase the risk of osteoporosis in rheumatoid arthritis female patients? Clin Rheumatol. May;27(5):565-572, 2008. https://doi.org/10.1007/s10067-007-0747-2
  13. 유주열. 동의사상의학강좌. 서울, 대성문화사, p 414, 1999.
  14. Jiang, Y., Choi, H.G., Li, Y., Park, Y.M., Lee, J.H., Kim, D.H., Lee, J.H., Son, J.K., Na, M., Lee, S.H. Chemical constituents of Cynanchum wilfordii and the chemotaxonomy of two species of the family Asclepiadacease, C. wilfordii and C. auriculatum. Arch Pharm Res. Dec;34(12):2021-2027, 2011. https://doi.org/10.1007/s12272-011-1203-z
  15. Lee, M.K., Yeo, H., Kim, J., Kim, Y.C. Protection of rat hepatocytes exposed to CCl4 in-vitro by cynandione A, a biacetophenone from Cynanchum wilfordii. J Pharm Pharmacol. Mar;52(3):341-345, 2000. https://doi.org/10.1211/0022357001773896
  16. Lee, M.K., Yeo, H., Kim, J., Markelonis, G.J., Oh, T.H., Kim, Y.C. Cynandione A from Cynanchum wilfordii protects cultured cortical neurons from toxicity induced by H2O2, L-glutamate, and kainate. J Neurosci Res. Jan 15;59(2):259-264, 2000. https://doi.org/10.1002/(SICI)1097-4547(20000115)59:2<259::AID-JNR12>3.0.CO;2-3
  17. Dougall, W.C., Glaccum, M., Charrier, K., Rohrbach, K., Brasel, K., De medt, T., Daro, E., Smith, J., Tometsko, M.E., Maliszewski, C.R., Armstrong, A., Shen, V., Bain, S., Cosman, D., Anderson, D., Morrissey, P.J., Peschon, J.J., Schuh, J. RANK is essential for osteoclast and lymph node development. Genes & Development 13: 2412-2424, 1999. https://doi.org/10.1101/gad.13.18.2412
  18. Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J., Wagner, E.F., Mak, T.W., Kodama, T., Taniguchi, T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Developmental Cell 3: 889-901, 2002. https://doi.org/10.1016/S1534-5807(02)00369-6
  19. Galibert, L., Tometsko, M.E., Anderson, D.M., Cosman, D., Dougall, W.C. The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-${\kappa}B$, a member of the TNFR superfamily. J Biol Chem 273: 34120-34127, 1998. https://doi.org/10.1074/jbc.273.51.34120
  20. Shimizu, H., Nakagami, H., Tsukamoto, I., Morita, S., Kunugiza, Y., Tomita, T., Yoshikawa, H., Kaneda, Y., Ogihara, T., Morishita, R. NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts. Gene Ther. Jun; 13(12):933-941, 2006. https://doi.org/10.1038/sj.gt.3302711