Korean Journal of Acupuncture

Society for Meridian and Acupoint (경락경혈학회)
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Psoraleae Semen Ethanol Extract Inhibits RANKL-Induced Osteoclast Differentiation and Osteoclast Specific Genes Expression

보골지 추출물이 파골세포 분화 및 골흡수 관련 유전자 발현에 미치는 영향

  • Ryu, Gwang-hyun (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Eom Ji (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Minsun (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Jae-Hyun (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Yujin (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Jin, Dae-hwan (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Sohn, Youngjoo (Department of Anatomy, College of Korean Medicine, Kyung Hee University) ;
  • Jung, Hyuk-Sang (Department of Anatomy, College of Korean Medicine, Kyung Hee University)
  • 류광현 (경희대학교 한의과대학 해부학교실) ;
  • 김엄지 (경희대학교 한의과대학 해부학교실) ;
  • 김민선 (경희대학교 한의과대학 해부학교실) ;
  • 김재현 (경희대학교 한의과대학 해부학교실) ;
  • 이유진 (경희대학교 한의과대학 해부학교실) ;
  • 진대환 (경희대학교 한의과대학 해부학교실) ;
  • 손영주 (경희대학교 한의과대학 해부학교실) ;
  • 정혁상 (경희대학교 한의과대학 해부학교실)
  • Received : 2021.08.10
  • Accepted : 2021.09.13
  • Published : 2021.09.27
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Abstract

Objectives : The increase of osteoclasts could cause osteoporosis and bone-related diseases. Also, the inhibition of osteoclast differentiation is important in treating bone-related diseases. Traditionally, Psoraleae Semen has been used for geriatric diseases, aging and musculoskeletal diseases. The purpose of this study is to investigate the effect of Psoraleae Semen ethanol extract (PS) on osteoclast differentiation and its function. Methods : To confirm the effect of PS on osteoclastogenesis and bone resorption activity, various levels of concentrations of PS (5, 10, 20 and 40 ㎍/ml) were tested on RAW 264.7 cells cultured with RANKL. We measured tartarate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity, pit formation and F-actin ring formation. The expressions of nuclear factor of activated T-cells (NFATc1) and c-Fos were confirmed through western blot and reverse transcription- polymerase chain reaction (RT-PCR). Also, the expression of bone resorption and fusion-related genes in osteoclast was confirmed by RT-PCR. Results : PS decreased the number of TRAP-positive cells and the TRAP activity. In addition, PS significantly inhibited the formation of pit and F-actin ring. Furthermore, PS decreased the expression of osteoclast related genes. Conclusions : PS inhibits osteoclast differentiation and bone resorption ability through inhibition of the expression of osteoclast-related genes. This indicates that PS may be a potential therapeutic agent to osteoporosis by suppressing osteoclastogenesis.

Keywords

Acknowledgement

본 연구는 보건복지부의 재원으로 한국보건산업진흥원의 보건의료기술연구개발사업 지원에 의하여 이루어진 것임(과제고유번호 : HF21C0092).

References

  1. Lane JM, Russell L, Khan SN. Osteoporosis. Clinical Orthopaedics and Related Research. 2000 ; (372) : 139-50. https://doi.org/10.1097/00003086-200003000-00016
  2. Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science. 2000 ; 289(5484) : 1508-14. https://doi.org/10.1126/science.289.5484.1508
  3. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003 ; 423(6937) : 337-42. https://doi.org/10.1038/nature01658
  4. Wagner EF, Karsenty G. Genetic control of skeletal development. Curr Opin Genet Dev. 2001 ; 11(5) : 527-32. https://doi.org/10.1016/s0959-437x(00)00228-8
  5. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002 ; 2(4) : 389-406. https://doi.org/10.1016/s1534-5807(02)00157-0
  6. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulaton of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999 ; 20(3) : 345-57. https://doi.org/10.1210/edrv.20.3.0367
  7. Nakashima T, Hayashi M, Takayanagi H. New insights into osteoclastogenic signaling mechanisms. Trends Endocrinol Metab. 2012 ; 23(11) : 582-90. https://doi.org/10.1016/j.tem.2012.05.005
  8. Huang H, Chang EJ, Ryu J, Lee ZH, Lee Y, Kim HH. Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway. Biochem Biophys Res Commun. 2006 ; 351(1) : 99-105. https://doi.org/10.1016/j.bbrc.2006.10.011
  9. Kim JH, Kim N. Regulation of NFATc1 in Osteoclast Differentiation. J Bone Metab. 2014 ; 21(4) : 233-41. https://doi.org/10.11005/jbm.2014.21.4.233
  10. Kim K, Lee SH, Kim JH, Choi Y, Kim N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol Endocrinol. 2008 ; 22(1) : 176-85. https://doi.org/10.1210/me.2007-0237
  11. Reid IR. Bisphosphonates in the treatment of osteoporosis: a review of their contribution and controversies. Skeletal Radiol. 2011 ; 40(9) : 1191-6. https://doi.org/10.1007/s00256-011-1164-9
  12. McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med. 2013 ; 126(1) : 13-20. https://doi.org/10.1016/j.amjmed.2012.06.023
  13. Kim JY, Song YS. East-West medical examination of osteoporosis. J Korean Med Rehabil. 1996 ; 6(1) : 293-315.
  14. Medical College of Nanjing University of Traditional Chinese Medicine. Interpretation of the Yellow Emperor's Internal Classics. Shanghai. Shanghai Science and Technology Press. 1983 : 4-5.
  15. Herbology Editorial Committee of Korean Medicine : Herbology. Younglimsa 2009 ; 607-8.
  16. Oh MS, Kim DR, Kim SY, Chang MS, Park SK. Antioxidant Effects of Psoraleae Fructus in GC-1 Cells. J Physiol Pathol Korean Med. 2005 ; 19(1) : 81-6.
  17. Jeong JC, Jang YS, Min GW. Peroxynitrite Scavenging Mechanism of Psoralea corylifolia. J Int Korean Med. 2004 ; 25(2) : 268-76.
  18. Park YK, Kang BS. Effects of Psoraleae Semen on Antioxidation in Rat's liver. Kor J Herbol. 1996 ; 11(2) : 101-14.
  19. Seo BI, Kim SH. A Study on the Effects of Allii Tuberosi Semen in Ovariectomized Osteoporosis of Rats. Herbal Formula Science. 1997 ; 5(1) : 179-83.
  20. Angel NZ, Walsh N, Forwood MR, Ostrowski MC, Cassady AI, Hume DA. Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover. J Bone Miner Res. 2000 ; 15(1): 103-10. https://doi.org/10.1359/jbmr.2000.15.1.103
  21. Charles JF, Aliprantis AO. Osteoclasts: more than 'bone eaters'. Trends Mol Med. 2014 ; 20(8) : 449-59. https://doi.org/10.1016/j.molmed.2014.06.001
  22. Rumpler M, Wurger T, Roschger P, Zwettler E, Sturmlechner I, Altmann P, et al. Osteoclasts on Bone and Dentin In Vitro: Mechanism of Trail Formation and Comparison of Resorption Behavior. Calcif Tissue Int. 2013 ; 93(6) : 526-39. https://doi.org/10.1007/s00223-013-9786-7
  23. Zhao Q, Wang X, Liu Y, He A, Jia R. NFATc1: functions in osteoclasts. Int J Biochem Cell Biol. 2010 ; 42(5) : 576-9. https://doi.org/10.1016/j.biocel.2009.12.018
  24. Winslow MM, Pan M, Starbuck M, Gallo EM, Deng L, Karsenty G, et al. Calcineurin/NFAT signaling in osteoblasts regulates bone mass. Dev Cell. 2006 ; 10(6) : 771-82. https://doi.org/10.1016/j.devcel.2006.04.006
  25. Arai A, Mizoguchi T, Harada S, Kobayashi Y, Nakamichi Y, Yasuda H, et al. Fos plays an essential role in the upregulation of RANK expression in osteoclast precursors within the bone microenvironment. J Cell Sci. 2012 ; 125(Pt 12) : 2910-7. https://doi.org/10.1242/jcs.099986
  26. 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
  27. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999 ; 13(18) : 2412-24. https://doi.org/10.1101/gad.13.18.2412
  28. Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int J Mol Sci. 2016 ; 17(6) : 868. https://doi.org/10.3390/ijms17060868
  29. Lehenkari P, Hentunen TA, Laitala-Leinonen T, Tuukkanen J, Vaananen HK. Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+. Exp Cell Res. 1998 ; 242(1) : 128-37. https://doi.org/10.1006/excr.1998.4071
  30. Nemeth K, Schoppet M, Al-Fakhri N, Helas S, Jessberger R, Hofbauer LC, et al. The role of osteoclast-associated receptor in osteoimmunology. J Immunol. 2011 ; 186(1) : 13-8. https://doi.org/10.4049/jimmunol.1002483
  31. Barrow AD, Raynal N, Andersen TL, Slatter DA, Bihan D, Pugh N, et al. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest. 2011 ; 121(9) : 3505-16. https://doi.org/10.1172/JCI45913
  32. Kodama J, Kaito T. Osteoclast Multinucleation: Review of Current Literature. Int J Mol Sci. 2020 ; 21(16) : 5685. https://doi.org/10.3390/ijms21165685
  33. Wu H, Xu G, Li YP. Atp6v0d2 is an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption. J Bone Miner Res. 2009 ; 24(5) : 871-85. https://doi.org/10.1359/jbmr.081239
  34. Chiu YH, Ritchlin CT. DC-STAMP: A Key Regulator in Osteoclast Differentiation. J Cell Physiol. 2016 ; 231(11) : 2402-7. https://doi.org/10.1002/jcp.25389
  35. Courtial N, Smink JJ, Kuvardina ON, Leutz A, Gothert JR, Lausen J. Tal1 regulates osteoclast differentiation through suppression of the master regulator of cell fusion DC-STAMP. FASEB J. 2012 ; 26(2) : 523-32. https://doi.org/10.1096/fj.11-190850