파골세포 분화에 목향 물 추출물의 효과

Effect of Water Extract of Saussureae Radix in RANKL-induced Osteoclast Differentiation

  • 이명수 (원광대학교 의과대학 류마티스내과학교실 및 원광의과학 연구소) ;
  • 김정중 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 오재민 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 최민규 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 송미진 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 안용환 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 이정휴 (원광대학교 의과대학 해부학교실 및 환경과학) ;
  • 전병훈 (원광대학교 한의과대학 병리학교실) ;
  • 박기인 (전북대학교 자연과학대학 생물학과) ;
  • 장성조 (원광대학교 의과대학 신경외과학교실)
  • Lee, Myeung-Su (Department of Internal Medicine, Division of Rheumatology and Institute of Wonkwang Medical Science) ;
  • Kim, Jeong-Joong (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Oh, Jae-Min (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Choi, Min-Kyu (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Song, Mi-Jin (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Ahn, Yong-Hwan (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Lee, Jeong-Hugh (Department of Anatomy, University of Wonkwang College of Medicine) ;
  • Jeon, Byung-Hoon (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Park, Kie-In (Division of Biological Science, School of Natural Science, Chonbuk National University) ;
  • Jang, Sung-Jo (Department of Neurosurgery, University of Wonkwang College of Medicine)
  • 투고 : 2011.05.06
  • 심사 : 2011.06.09
  • 발행 : 2011.06.25

초록

Osteoporosis is social problem around the world, because fracture of old age may lead to critical medical condition. Osteoclast is a main target for prevention and treatment of osteoporosis due to their responsibility for bone resorption. Saussureae Radix has been known that has gastro-protective, bronchodilatory effect and has a anti-biotic effect. Saussureae Radix has been widely used in Oriental medicine. However, the effect of extract of Saussureae Radix in osteoclast differentiation remains unknown. Thus, we examined the effect of Saussureae Radix in receptor activator of nuclear factor-${\kappa}$B ligand (RANKL)-induced osteoclast differentiation. From the results of our study, Here we found that Saussureae Radix significantly inhibited osteoclast differentiation induced by RANKL. Saussureae Radix suppressed the activation of NF${\kappa}$B in bone marrow macrophages (BMMs) treated with RANKL. Also, Saussureae 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, Saussureae Radix greatly inhibited the protein expression of c-fos and NFATc1. especially in the case of NFATc1 expression, a master transcription factor of the differentiation of osteoclasts is very important step for osteoclastogenesis. These results demonstrate that Saussureae Radix may be useful treatment option of bone-related disease such as osteoporosis and rheumatoid arthritis.

키워드

참고문헌

  1. Kanis, J.A., Oden, A., Johnell, O., De Laet, C., Jonsson, B., Oglesby, A.K. The components of excess mortality after hip fracture. Bone 32: 468, 2003. https://doi.org/10.1016/S8756-3282(03)00061-9
  2. Melton, L.J., 3rd, Atkinson, E.J., O'Connor, M.K., et al. Bone density and fracture risk in men. J Bone Miner Res 13: 1915, 1998. https://doi.org/10.1359/jbmr.1998.13.12.1915
  3. Johnell, O. and Kanis, J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17: 1726, 2006. https://doi.org/10.1007/s00198-006-0172-4
  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. Abrahamsen, B. Bisphosphonate adverse effects, lessons from large databases. Curr Opin Rheumatol. 22(4):404-409, 2010. https://doi.org/10.1097/BOR.0b013e32833ad677
  6. Kwak, H.B., Kim, J.H., Kim, D.J., Kwon, Y.M., Oh, J., Kim, Y.K. Effect of water extract of deer antler in osteoclast differentiation. Korean J Oriental Physiology & pathology. 22: 891-895, 2008.
  7. 정연태, 최윤홍, 송정훈, 이창훈, 오재민. 두충의 물 추출물이 파골세포의 분화에 미치는 영향. 동의생리병리학회지 23: 613-618, 2009.
  8. Deriu, A., Zanetti, S., Sechi, L.A., Marongiu, B., Piras, A., Porcedda, S., Tuveri, E. Antimicrobial activity of Inula helenium L. essential oil against Gram-positive and Gram-negative bacteria and Candida spp. Int J Antimicrob Agents. 31(6):588-590, 2008. https://doi.org/10.1016/j.ijantimicag.2008.02.006
  9. Seo, J.Y., Lim, S.S., Kim, J.R., Lim, J.S., Ha, Y.R., Lee, I.A., Kim, E.J., Park, J.H., Kim, J.S. Nrf2-mediated induction of detoxifying enzymes by alantolactone present in Inula helenium. Phytother Res. 22(11):1500-1505, 2008. https://doi.org/10.1002/ptr.2521
  10. Dorn, D.C., Alexenizer, M., Hengstler, J.G., Dorn, A. Tumor cell specific toxicity of Inula helenium extracts. Phytother Res. 20(11):970-980, 2006. https://doi.org/10.1002/ptr.1991
  11. Boyle, W.J., Simonet, W.S., Lacey, D.L. Osteoclast differentiation and activation. Nature. 423: 337-342, 2003. https://doi.org/10.1038/nature01658
  12. Rao, A., Luo, C., Hogan, P.G. Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15: 707-747, 1997. https://doi.org/10.1146/annurev.immunol.15.1.707
  13. Takayanagi, H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat. Rev. Immunol. 7: 292-304, 2007. https://doi.org/10.1038/nri2062
  14. Vestergaard, P., Schwartz, K., Pinholt, E.M., Rejnmark, L., Mosekilde, L. Risk of atrial fibrillation associated with use of bisphosphonates and other drugs against osteoporosis: a cohort study. Calcif Tissue Int. 86(5):335-342, 2010. https://doi.org/10.1007/s00223-010-9349-0
  15. Watts, N.B., Diab, D.L. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 95(4):1555-1565, 2010. https://doi.org/10.1210/jc.2009-1947
  16. 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. 13(12):933-941, 2006. https://doi.org/10.1038/sj.gt.3302711