Effects of Gastrodia elata Blune Water Extract on RANKL-induced Osteoclast Differentiation

천마가 RANKL에 의해 유도된 파골세포의 분화에 미치는 효과

  • Choi, Yun-Hong (Department of Anatomy & Institute for Environmental Science, Wonkwang University) ;
  • Song, Jeong-Hoon (Department of Plastic & Reconstructive Surgery, Wonkwang University) ;
  • Jang, Sung-Jo (Department of Neurosurgery, School of Medicine, Wonkwang University) ;
  • Kim, Jin-Kook (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Choi, Min-Kyu (Department of Anatomy & Institute for Environmental Science, Wonkwang University)
  • 최윤홍 (원광대학교 의과대학 해부학교실 및 환경과학연구소) ;
  • 송정훈 (원광대학교 의과대학 성형외과학교실) ;
  • 장성조 (원광대학교 의과대학 신경외과학교실) ;
  • 김진국 (원광대학교 한의과대학 병리학교실) ;
  • 최민규 (원광대학교 의과대학 해부학교실 및 환경과학연구소)
  • Received : 2010.09.14
  • Accepted : 2010.10.15
  • Published : 2010.10.25

Abstract

Impairment of balance between bone-resorbing osteoclasts and bone-forming osteoblasts result in bone disease. Especially, increased osteoclast formation and activity are responsible for bone diseases such as osteoporosis, rheumatoid arthritis, periodontal disease. Natural metabolites of plants have recently received much attention as an alternative tools for the development of novel therapeutic strategy. The aim of this study was to search the natural products to inhibit osteoclast differentiation and was to evaluate of its mechanism. Water extract of Gastrodia elata Blune significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs) in a dose dependent manner. However, water extract of Gastrodia elata Blune did not affect cytotoxicity when compared with control. The mRNA expression of c-Fos, NFATc1, and TRAP induced by RANKL was inhibited by water extract of Gastrodia elata Blune treatment. Also, water extract of Gastrodia elata Blune inhibited the protein expression of c-Fos and NFATc1 expression in BMMs treated with RANKL. Water extract of Gastrodia elata Blune suppressed the phosphorylation of p38 induced by RANKL. In general, RANKL considerably inhibited the expression level of Id2 and MafB known as negative regulators of osteoclastogenesis, but RANKL did not inhibit Id2 and MafB expression in BMMs when it was co-treated with Gastrodia elata Blune. Taken together, these results suggest that Gastrodia elata Blune may be a useful drug in the treatment of bone-related disease.

Keywords

References

  1. Melton, L.J. 3rd. Who has osteoporosis? A conflict between clinical and public health perspectives. J. Bone Miner. Res. 15: 2309-2314, 2000. https://doi.org/10.1359/jbmr.2000.15.12.2309
  2. Halasy-Nagy, J.M., Rodan, G.A., Reszka, A. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone 29: 553-559, 2001. https://doi.org/10.1016/S8756-3282(01)00615-9
  3. Kwak, H.B., Kim, J.Y., Kim, K.J., Choi, M.K., Kim, J.J. Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss. Biol. Pharm. Bull. 32: 1193-1198, 2009. https://doi.org/10.1248/bpb.32.1193
  4. Khosla, S., Burr, D., Cauley, J., Dempster, D.W., Ebeling, P.R. Felsenberg, D., Gagel, R.F., Gilsanz, V., Guise, T., Koka, S., McCauley, L.K., McGowan, J., McKee, M.D., Mohla, S., Pendrys, D.G., Raisz, L.G., Ruggiero, S.L., Shafer, D.M., Shum, L., Silverman, S.L., Van Poznak, C.H., Watts, N., Woo, S.B., Shane, E. 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
  5. Oh, S., Kyung, T.W., Choi, H.S. Curcumin inhibits osteoclastogenesis by decreasing receptor activator of nuclear factor-kappaB ligand (RANKL) in bone marrow stromal cells. Mol. Cells 26: 486-489, 2008.
  6. Park, C.K., Kim, H.J., Kwak, H.B., Lee, T.H., Bang, M.H., Kim, C.M., Lee, Y., Chung, D.K., Baek, N.I., Kim, J., Lee, Z.H., Kim, H.H. Inhibitory effects of Stewartia koreana on osteoclast differentiation and bone resorption. Int. Immunopharmacol. 7: 1507-1516, 2007. https://doi.org/10.1016/j.intimp.2007.07.016
  7. Kwak, H.B., Yang, D., Ha, H., Lee, J.H., Kim, H.N., Woo, E.R., Lee, S., Kim, H.H., Lee, Z.H. Tanshinone IIA inhibits osteoclast differentiation through down-regulation of c-Fos and NFATc1. Exp. Mol. Med. 38: 256-264, 2006. https://doi.org/10.1038/emm.2006.31
  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. Huang, Z.L. Recent developments in pharmacological study and clinical application of Gastrodia elata in China. Zhong. Xi. Yi. Jie. He. Za. Zhi. 5: 251-254, 1985.
  10. Li, N., Wang, K.J., Chen, J.J., Zhou, J. Phenolic compounds from the rhizomes of Gastrodia elata. J. Asian Nat. Prod. Res. 9: 373-377, 2007. https://doi.org/10.1080/10286020600780979
  11. Yeung Him-Che. Handbook of Chinese herbs and formulas. Institute of Chinese Medicine, Los Angeles 1985.
  12. Bown, D. Encyclopaedia of herbs and their uses. Dorling Kindersley, London. 1995.
  13. Duke, J.A., Ayensu, E.S. Medicinal plants of China. 1985.
  14. Boyle, W.J., Simonet, W.S., Lacey, D.L. Osteoclast differentiation and activation. Nature, 423: 337-342, 2003. https://doi.org/10.1038/nature01658
  15. Teitelbaum, S.L., Ross, F.P. Genetic regulation of osteoclast development and function. Nat. Rev. Genet. 4: 638-649, 2003. https://doi.org/10.1038/nrg1122
  16. Lee, S.E., Woo, K.M., Kim, S.Y., Kim, H.M., Kwack, K., Lee, Z.H., Kim, H.H. The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 1: 71-77, 2002.
  17. Tanaka, S., Miyazaki, T., Fukuda, A., Akiyama, T., Kadono, Y., Wakeyama, H., Kono, S., Hoshikawa, S., Nakamura, M., Ohshima, Y., Hikita, A., Nakamura, I., Nakamura, K. Molecular mechanism of the life and death of the osteoclast. Ann. N. Y. Acad. Sci. 1068: 180-186, 2006. https://doi.org/10.1196/annals.1346.020
  18. Huang, H., Chang, E.J., Ryu, J., Lee, Z.H., Lee, Y., Kim, H.H. Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway. Biochem. Biophys. Res. Commun. 351: 99-105, 2006. https://doi.org/10.1016/j.bbrc.2006.10.011
  19. Chang, E.J., Ha, J., Huang, H., Kim, H.J., Woo, J.H., Lee, Y., Lee, Z.H., Kim, J.H., Kim, H.H. The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation. J. Cell Sci. 121: 2555-2564, 2008. https://doi.org/10.1242/jcs.028217
  20. Kim, K., Lee, S.H., Kim J.H., Choi, Y., Kim, N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol. Endocrinol. 22: 176-185, 2008. https://doi.org/10.1210/me.2007-0237
  21. 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. Developmental Cell, 3: 889-901, 2002. https://doi.org/10.1016/S1534-5807(02)00369-6
  22. Lee, J., Kim, K., Kim, J.H., Jin, H.M., Choi, H.K., Lee, S.H., Kook, H., Kim, K.K., Yokota, Y., Lee, S.Y., Choi, Y., Kim, N. Id helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation. Blood 107: 2686-2693, 2006. https://doi.org/10.1182/blood-2005-07-2798
  23. Kim, K., Kim, J., Lee, J., Kim, K., Lee, S., Kim, N. MafB negatively regulates RANKL-mediated osteoclast differentiation. Blood 109: 3253-3259, 2007. https://doi.org/10.1182/blood-2006-09-048249
  24. Merkel, K.D., Erdmann, J.M., McHugh, K.P., Abu-Amer, Y., Ross, F.P., Teitelbaum, S.L. Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am. J. Pathol. 154: 203-210, 1999. https://doi.org/10.1016/S0002-9440(10)65266-2
  25. Liu, X.D., Zhu, Y.K., Umino, T., Spurzem, J.R., Romberger, D.J., Wang, H., Reed, E., Rennard, S.I. Cigarette smoke inhibits osteogenic differentiation and proliferation of human osteoprogenitor cells in monolayer and three-dimensional collagen gel culture. J. Lab. Clin. Med. 137: 208-219, 2001. https://doi.org/10.1067/mlc.2001.113066
  26. Redlich, K., Hayer, S., Ricci, R., David, J.P., Tohidast-Akrad, M., Kollias, G., Steiner, G. Smolen, J.S. Wagner, E.F., Schett, G. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J. Clin. Invest. 110: 1419-1427, 2002. https://doi.org/10.1172/JCI0215582
  27. Lee, J.H., Jin, H., Shim, H.E., Kim, H.N., Ha, H., Lee, Z.H. Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-kappaB signal. Mol. Pharmacol. 77: 17-25, 2010. https://doi.org/10.1124/mol.109.057877
  28. Dougall, W.C., Glaccum, M., Charrier, K., Rohrbach, K., Brasel, K., De Smedt, 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 Dev. 13: 2412-2424, 1999. https://doi.org/10.1101/gad.13.18.2412
  29. 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
  30. Asagiri, M., Sato, K., Usami, T., Ochi, S., Nishina, H., Yoshida, H., Morita, I., Wagner, E.F., Mak, T.W., Serfling, E., Takayanagi, H. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J. Exp. Med. 202: 1261-1269, 2005. https://doi.org/10.1084/jem.20051150
  31. Matsuo, K., Galson, D.L., Zhao, C., Peng, L., Laplace, C., Wang, K.Z., Bachler, M.A., Amano, H., Aburatani, H., Ishikawa, H., Wagner, E.F. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-fos. J. Biol. Chem. 279: 26475-26480, 2004. https://doi.org/10.1074/jbc.M313973200
  32. 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
  33. Sieweke, M., Tekotte, H., Frampton, J., Graf, T. MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation. Cell 85: 49-60, 1996. https://doi.org/10.1016/S0092-8674(00)81081-8