Korean Journal of Acupuncture

Society for Meridian and Acupoint (경락경혈학회)
권호 표지
DOI QR코드

DOI QR Code

Forsythiae Fructus Extract Inhibits RANKL-Induced Osteoclast Differentiation and Prevent Bone Loss in OVX-Induced Osteoporosis Rat

연교의 파골세포 분화 및 골 흡수 억제 기전 연구

  • Eom, Ji-Whan (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Jae-Hyun (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Minsun (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Sangwoo (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Shin, Hwajeong (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Jung, Hyuk-Sang (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Sohn, Youngjoo (Department of Anatomy, College of Korean Medicine, Kyung Hee University)
  • 엄지환 (경희대학교 한의과대학 해부학교실) ;
  • 김재현 (경희대학교 한의과대학 해부학교실) ;
  • 김민선 (경희대학교 한의과대학 해부학교실) ;
  • 김상우 (경희대학교 한의과대학 해부학교실) ;
  • 신화정 (경희대학교 한의과대학 해부학교실) ;
  • 정혁상 (경희대학교 한의과대학 해부학교실) ;
  • 손영주 (경희대학교 한의과대학 해부학교실)
  • Received : 2019.03.21
  • Accepted : 2019.05.01
  • Published : 2019.06.27
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Osteoporosis is a condition characterized by low bone mass and increased bone fragility. It has become a major problem of senior citizens. The purpose of this study is to experiment the effect of water extract of Forsythiae Fructus (wFF) on osteoclast differentiation; and the other purpose is to examine the effect of wFF on osteoporosis in ovariectomized rat. Methods : To investigate the effect of wFF on osteoclast differentiation and activity, RAW 264.7 cells were used. The number of TRAP positive cell, TRAP activity, pit area, mRNA expression of makers (RANK, TRAP, CA II, CTK, MMP-9, NFATc1, c-Fos), protein expression of makers (NFATc1, c-Fos) were investigated. For in vivo study, 40 female Sprague-Dawley (SD) rats were induced osteoporosis by ovariectomy (OVX) and then tested for anti-osteoporosis effect by administration of wFF. Results : wFF suppressed osteoclatogenesis, TRAP activity and pit area formation. Moreover, wFF decreased the expression of master differentiation factors (NFATc1, c-Fos) and also reduced the osteoclastogenesis-related markers (TRAP, CA II, CTK, MMP-9). These suggest that wFF inhibit osteoclasts differentiation and bone resorption. In the OVX rat model, wFF inhibited decreasing of BMD and trabecular area. Conclusions : Forsythiae Fructus should be effective for osteoporosis prevention and treatment.

Keywords

References

  1. Alliston T, Derynck R. Interfering with bone remodelling. Nature. 2002 ; 416(6882) : 686-7. https://doi.org/10.1038/416686a
  2. Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science. 2000 ; 289(5484) : 1501-4. https://doi.org/10.1126/science.289.5484.1501
  3. Consensus A. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 ; 94(6) : 646-50. https://doi.org/10.1016/0002-9343(93)90218-E
  4. Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol. 2017 ; 4(1) : 46-56. https://doi.org/10.5152/eurjrheum.2016.048
  5. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992 ; 2 : 285-9. https://doi.org/10.1007/BF01623184
  6. Kennel KA and Drake MT. Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management. Mayo Clin Proc. 2009 ; 84(7) : 632-8. https://doi.org/10.4065/84.7.632
  7. Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995 ; 332 : 1589-93. https://doi.org/10.1056/NEJM199506153322401
  8. Arron JR, Choi Y. Bone versus immune system. Nature. 2000 ; 408 : 535-6. https://doi.org/10.1038/35046196
  9. Lorenzo J. Interactions between immune and bone cells: new insights with many remaining questions. J Clin Invest. 2000 ; 106 : 749-52. https://doi.org/10.1172/JCI11089
  10. Ginaldi L, Di Benedetto MC, De Martinis M. Osteoporosis, inflammation and ageing. Immun Ageing. 2005 ; 2(1) : 14. https://doi.org/10.1186/1742-4933-2-14
  11. Bae BC, The yellow emperor's classic. Seoul: Seongbosa 1994 ; 292-5, 383-7.
  12. Shim SD, Ahn DK. Effects of the Cerbi Cornu on the Aged Ovariectomized Rat Model of Postmenopausal Osteoporosis. Kor. J. Herblogy. 1998 ; 13(1) : 1-23.
  13. Joo SJ, Park JH, Seo B. Effects of Korean Corni Fructus On treatment of Osteoporosis In Ovariectomized Rats. Kor. J. Herblogy. 2007 ; 22(2) : 83-95.
  14. Choi JK, Yoo DY. The effect of Kamijoaguiem on Osteoporosis Induced by Ovariectomy in Rats, J Orient Obstet Gynecol. 2006 ; 19(2) : 107-26.
  15. Choi HS. The Efficacy of Cynomorii Herba and Eucommiae Cortex on Treatment of Osteoporosis in Ovariectomized Rats. Kor. J. Herbology. 2008 ; 23(2) : 19-24.
  16. Lee JA, Yang SJ, Cho SH, Jin CS, Ban HR. Effects of the rehmanniae radix preparat on osteoporotic rats induced by ovariectomy. J Orient Obstet Gynecol. 2004 ; 17(4) : 112-24.
  17. Ministry of Food and Drug Safety. Korean Pharmacopoeia appendix #2. 2019 ; 11 : 72-3.
  18. Lee JM, Choi SW, Cho SH, Rhee SJ. Effect of Forsythia Viridissima Extracts on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet. J Nutr Health. 2003 ; 36(10) : 990-6.
  19. Bao J, Ding R, Zou L, Zhang C, Wang K, Liu F, et al. Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation. Am J Chin Med. 2016 ; 44(5) : 1043-61. https://doi.org/10.1142/S0192415X16500580
  20. You BJ, Kim HT. Effect of Forsythiae Fructus Exract on the Release of Inflammatory Mediatorinduced by Lipopolysaccharide in RAW 264.7 Macrophage. J Physiol & Pathol Korean Med. 2007 ; 21(3) : 765-70.
  21. Lim H, Lee JG, Lee SH, Kim YS, Kim HP. Anti-inflammatory activity of phylligenin, a lignan from the fruits of Forsythia koreana, and its cellular mechanism of action. J Ethnopharmacol. 2008 ; 118(1) ; 113-7. https://doi.org/10.1016/j.jep.2008.03.016
  22. Schinella GR, Tournier HA, Prieto JM, Mordujovich D, Rios JL. Antioxidant activity of anti-inflammatory plant extracts. Life Sci. 2002 ; 70(9) : 1023-33. https://doi.org/10.1016/S0024-3205(01)01482-5
  23. Lee EB, Keum HJ. Pharmacological studieson Forsythiae Fructus. Kor J Pharmacogn. 1998 ; 19(4) : 262-9.
  24. Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest. 2011 ; 41(12) : 1361-6. https://doi.org/10.1111/j.1365-2362.2011.02545.x
  25. Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017 ; 14(2) : 209-16. https://doi.org/10.11138/ccmbm/2017.14.1.209
  26. Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewicz-Sapuntzakis M, Guo P, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr. 1996 ; 126 : 161-7. https://doi.org/10.1093/jn/126.1.161
  27. Dong Z, Lu X, Tong X, Dong Y, Tang L, Liu M. Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics. Molecules. 2017 ; 22(9). https://doi.org/10.3390/molecules22091466
  28. Yoshitake H, Rittling SR, Denhardt DT, Noda M. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc Natl Acad Sci USA. 1999 ; 96(14) : 8156-60. https://doi.org/10.1073/pnas.96.14.8156
  29. Kirstein B, Chambers TJ, Fuller K. Secretion of tartrate-resistant acid phosphatase by osteoclasts correlates with resorptive behavior. J Cell Biochem. 2006 ; 98(5) : 1085-94. https://doi.org/10.1002/jcb.20835
  30. Kim SN, Kim MH, Kim YS, Ryu SY, Min YK, Kim SH. Inhibitory effect of (-)-saucerneol on osteoclast differentiation and bone pit formation. Phytother Res. 2009 ; 23(2) : 185-91. https://doi.org//10.1002/ptr.2581
  31. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 1999 ; 96(7) : 3540-5. https://doi.org/10.1073/pnas.96.7.3540
  32. Teiteilbaum SL. Bone resorption by osteoclast. Science. 2000 ; 289(5484) : 1504-8. https://doi.org/110.1126/science.289.5484.1504
  33. Karhukorpi EK. Carbonic anhydrase II in rat acid secreting cells: comparison of osteoclasts with gastric parietal cells and kidney intercalated cells. Acta Histochem. 1991 ; 90(1) : 11-20. https://doi.org/10.1016/S0065-1281(11)80151-0
  34. Drake FH, Dodds RA, James IE, Connor JR, Debouck C, Richardson S, et al. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem. 1996 ; 271(21) : 12511-16. https://doi.org/10.1074/jbc.271.21.12511
  35. Blavier L, Delaisse JM. Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones. J Cell Sci. 1995 ; 108(12) : 3649-59. https://doi.org/10.1242/jcs.108.12.3649
  36. Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003 ; 17(18) : 2205-32. https://doi.org/10.1101/gad.1102703
  37. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002 ; 3(6) : 889-901. https://doi.org/10.1016/S1534-5807(02)00369-6
  38. Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Miner. 1991 ; 15(3) : 175-191. https://doi.org/10.1016/0169-6009(91)90124-I

Cited by

  1. 진교의 파골세포 분화 및 골 흡수 유전자 억제기전 연구 vol.37, pp.2, 2020, https://doi.org/10.14406/acu.2020.002