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 Rubi Fructus in RANKL-induced Osteoclast Differentiation

파골세포 분화에 미치는 복분자 물 추출물의 효과

  • Oh, Jae-Min (Department of Anatomy, Wonkwang Medical Science) ;
  • Lee, Myeung-Su (Department of Internal Medicine, Division of Rheumatology and Institute of Wonkwang Medical Science) ;
  • Kim, Jeong-Joong (Department of Anatomy, Wonkwang Medical Science) ;
  • Lee, Jeong-Hugh (Department of Anatomy, Wonkwang Medical Science) ;
  • Chae, Soo-Uk (Department of Orthopedic Surgery, Division of Endocrinology and Metabolism, University of Wonkwang College of Medicine, Sanbon Medical Center) ;
  • Kim, Ha-Young (Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Wonkwang College of Medicine, Sanbon Medical Center) ;
  • Jeon, Byung-Hoon (Department of Pathology, College of Oriental Medicine, Wonkwang College of Medicine) ;
  • Park, Kie-In (Division of Biological Science, School of Natural Science, Chonbuk National University) ;
  • Moon, Seo-Young (Department of Anesthesiology and Pain Medicine, University of Wonkwang College of Medicine, Sanbon Medical Center) ;
  • Cho, Hae-Joong (Department of Obstetrics and Gynecology, University of Wonkwang College of Medicine)
  • 오재민 (원광대학교 의과대학 해부학교실) ;
  • 이명수 (원광대학교 의과대학 류마티스내과학교실 및 원광의과학 연구소) ;
  • 김정중 (원광대학교 의과대학 해부학교실) ;
  • 이정휴 (원광대학교 의과대학 해부학교실) ;
  • 채수욱 (원광대학교 의과대학 정형외과학교실) ;
  • 김하영 (원광대학교 산본병원 내분비내과학교실) ;
  • 전병훈 (원광대학교 한의과대학 병리학교실) ;
  • 박기인 (전북대학교 자연과학대학 생물학과) ;
  • 문서영 (원광대학교 산본병원 마취통증의학과) ;
  • 조해중 (원광대학교 산본병원 산부인과학교실)
  • Received : 2011.07.14
  • Accepted : 2011.08.09
  • Published : 2011.08.25
Download PDF
⟨ Previous Next ⟩

Abstract

To prevent and treat the osteoporotic fracture, more attention should be paid in old age patients. Osteoclast which has ability to bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Rubi Fructus has been widely used in Oriental medicine. Extracts of the leaves and fruit of Rubus species have been used in various countries as natural remedies to treat diabetes, infections, colic, and burns. However, the effect of extract of Rubi Fructus (fruit of Rubus coreanus Miq.) in osteoclast differentiation remains unknown. Thus, we evaluated the effect of Rubi Fructus on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation. Here we found that Rubi Fructus significantly inhibited osteoclast differentiation induced by RANKL. Rubi Fructus suppressed the activation of p38 pathway and NFkB in bone marrow macrophages (BMMs) treated with RANKL. Also, Rubi Fructus 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, Rubi Fructus 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. Taken together, our results demonstrated that Rubi Fructus may be useful treatment option of bone-related disease such as osteoporosis and rheumatoid arthritis.

Keywords

References

  1. 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
  2. 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
  3. Silverman, S.L., Lane, N.E. Glucocorticoid-induced osteoporosis. Curr Osteoporos Rep. 7(1):23-26, 2009. https://doi.org/10.1007/s11914-009-0005-4
  4. Lata, P.F., Elliott, M.E. Patient assessment in the diagnosis, prevention, and treatment of osteoporosis. Nutr Clin Pract 22(3):261-275, 2007. https://doi.org/10.1177/0115426507022003261
  5. 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
  6. Abrahamsen, B. Bisphosphonate adverse effects, lessons from large databases. Curr Opin Rheumatol 22(4):404-409, 2010. https://doi.org/10.1097/BOR.0b013e32833ad677
  7. 정연태, 최윤홍, 송정훈, 이창훈, 오재민. 두충의 물 추출물이 파골세포의 분화에 미치는 영향. 동의생리병리학회지 23(3):613-618, 2009.
  8. 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.
  9. Ju, H.K., Cho, E.J., Jang, M.H., Lee, Y.Y., Hong, S.S., Park, J.H., Kwon, S.W. Characterization of increased phenolic compounds from fermented Bokbunja (Rubus coreanus Miq.) and related antioxidant activity.J Pharm Biomed Anal. 49(3):820-827, 2009. https://doi.org/10.1016/j.jpba.2008.12.024
  10. Shin, T.Y., Kim, S.H., Lee, E.S., Eom, D.O., Kim, H.M. Action of Rubus coreanus extract on systemic and local anaphylaxis. Phytother Res. 16(6):508-513, 2002. https://doi.org/10.1002/ptr.925
  11. Do, S.H., Lee, J.W., Jeong, W.I., Chung, J.Y., Park, S.J., Hong, I.H., Jeon, S.K., Lee, I.S., Jeong, K.S. Bone-protecting effect of Rubus coreanus by dual regulation of osteoblasts and osteoclasts. Menopause. 15(1):676-683, 2008. https://doi.org/10.1097/gme.0b013e31815bb687
  12. 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 echanisms 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
  13. 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. 27(5):565-572, 2008. https://doi.org/10.1007/s10067-007-0747-2
  14. Abrahamsen, B. Adverse effects of bisphosphonates. Calcif Tissue Int. 86(6):421-435, 2010. https://doi.org/10.1007/s00223-010-9364-1
  15. Wang, B., Shin, X., Li, Y., Jia, Z. Pentacyclic triterpenoid glycosyl esters from Rubus pileatus. Phytochemistry 46: 559-563, 1997. https://doi.org/10.1016/S0031-9422(97)00314-2
  16. Park, J.H., Oh, S.M., Lim, S.S., et al. Induction of heme oxygenase-1 mediates the anti-inflammatory effects of the ethanol extract of Rubus coreanus in murine macrophages. Biochem Biophys Res Commun. 351: 146-152, 2006. https://doi.org/10.1016/j.bbrc.2006.10.008
  17. Saylor, P.J. Targeted therapies: Denosumab-a new option for solid tumors metastatic to bone. Nat Rev Clin Oncol. 8(6):322-334, 2011. https://doi.org/10.1038/nrclinonc.2011.70
  18. 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
  19. 이명수, 김정중, 오재민, 최민규, 송미진, 안용환, 이정휴, 전병훈, 박기인, 장성조. 파골세포 분화에 목향 물 추출물의 효과. 동의생리병리학회지 25(3):516-520, 2011.
  20. Erratum in. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol. 5(3):174, 2009. https://doi.org/10.1038/ncpendmet1039