DOI QR코드

DOI QR Code

Hexane-Soluble Fraction of the Common Fig, Ficus carica, Inhibits Osteoclast Differentiation in Murine Bone Marrow-Derived Macrophages and RAW 264.7 Cells

  • Park, Young-Ran (Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Eun, Jae-Soon (College of Pharmacy, Woosuk University) ;
  • Choi, Hwa-Jung (Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Nepal, Manoj (Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Kim, Dae-Keun (College of Pharmacy, Woosuk University) ;
  • Seo, Seung-Yong (College of Pharmacy, Woosuk University) ;
  • Li, Rihua (College of Pharmacy, Woosuk University) ;
  • Moon, Woo-Sung (Department of Pathology, School of Medicine, Chonbuk National University) ;
  • Cho, Nam-Pyo (Department of Oral Pathology, School of Dentistry, Chonbuk National University) ;
  • Cho, Sung-Dae (Department of Oral Pathology, School of Dentistry, Chonbuk National University) ;
  • Bae, Tae-Sung (Department of Dental Biomaterials, School of Dentistry, Chonbuk National University) ;
  • Kim, Byung-Il (Department of Materials Science and Metallurgical Engineering, Sunchon National University) ;
  • Soh, Yun-Jo (Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University)
  • Published : 2009.12.31

Abstract

Osteoclasts, derived from multipotent myeloid progenitor cells, play homeostatic roles in skeletal modeling and remodeling, but may also destroy bone in pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclast development depends critically on a differentiation factor, the receptor activator of NF-${\kappa}B$ ligand (RANKL). In this study, we found that the hexane soluble fraction of the common fig Ficus carica (HF6-FC) is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW264.7 cells and in bone marrow-derived macrophages (BMMs). HF6-FC exerts its inhibitory effects by suppression of p38 and NF-${\kappa}B$ but activation of ERK. In addition, HF6-FC significantly decreased the expression of NFATc1 and c-Fos, the master regulator of osteoclast differentiation. The data indicate that components of HF6-FC may have therapeutic effects on bone-destructive processes such as osteoporosis, rheumatoid arthritis, and periodontal bone resorption.

Keywords

References

  1. Ahmed W, Khan AQ, Malik A. Two Triterpenes from the Leaves of Ficus carica. Planta Med 54: 481, 1988 https://doi.org/10.1055/s-2006-962522
  2. Alliston T, Derynck R. Medicine: interfering with bone remodelling. Nature 416: 686-687, 2002 https://doi.org/10.1038/416686a
  3. Canal JR, Torres MD, Romero A, P$\'{e}$rez C. A chloroform extract obtained from a decoction of Ficus carica leaves improves the cholesterolaemic status of rats with streptootocin-includede diabetes. Acta Physiol Hung 87: 71-76, 2000 https://doi.org/10.1556/APhysiol.87.2000.1.8
  4. Chang EJ, Kim HJ, Ha J, Kim HJ, Ryu J, Park KH, Kim UH, Lee ZH, Kim HM, Fisher DE, Kim HH. Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4. J Cell Sci 120: 166-176, 2007 https://doi.org/10.1242/jcs.03310
  5. Choi HJ, Song BJ, Gong YD, Gwak WJ, Soh Y. Rapid degradation of hypoxia-inducible factor-1alpha by KRH102053, a new activator of prolyl hydroxylase 2. Br J Pharmacol 154: 114-125, 2008 https://doi.org/10.1038/bjp.2008.70
  6. Coon D, Gulati A, Cowan C, He J. The role of cyclooxygenase-2 (COX-2) in inflammatory bone resorption. J Endod 33: 432-436, 2007 https://doi.org/10.1016/j.joen.2006.12.001
  7. El-Kholy IS, Shaban MA. Constituents of the leaves of Ficus carica, L. II. Isolation of a psi­taraxasteryl ester, rutin, and a new steroid sapogenin. J Chem Soc Perkin 13: 1140-1142, 1966
  8. Han KY, Yang D, Chang EJ, Lee Y, Huang H, Sung SH, Lee ZH, Kim YC, Kim HH. Inhibition of osteoclast differentiation and bone resorption by sauchinone. Biochem Pharmacol 74: 911-923, 2007 https://doi.org/10.1016/j.bcp.2007.06.044
  9. Jimi E, Aoki K, Saito H, D'Acquisto F, May MJ, Nakamura I, Sudo T, Kojima T, Okamoto F, Fukushima H, Okabe K, Ohya K, Ghosh S. Selective in hibition of NF-kappa B block osteoclastogenesis and prevents inflammatory bone destructin in vivo. Nat Med 6: 617-624, 2004
  10. Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, Inoue J. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO 20: 1271-1280, 2001 https://doi.org/10.1093/emboj/20.6.1271
  11. Lee SE, Woo KM, Kim SY, Kim HM, Kwack K, Lee ZH, Kim HH. The phosphatidylinositol 3-kinase, p38, and extracellular signal- regulated kinase pathways are involved in osteoclast differentiation. Bone 30: 71-77, 2002 https://doi.org/10.1016/S8756-3282(01)00657-3
  12. Lee WT. Coloured standard illustrations of Korean plants. Academy press, Seoul, p 624, 1996
  13. Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J Clin Invest 115: 2625-2632, 2005 https://doi.org/10.1172/JCI26322
  14. Mino T, Sugiyama E, Taki H, Kuroda A, Yamashita N, Maruyama M, Kobayashi M. Interleukin-1alpha and tumor necrosis factor alpha synergistically stimulate prostaglandin E2-dependent production of interleukin-11 in rheumatoid synovial fibroblasts. Arthritis Rheum 41: 2004-2013, 1998 https://doi.org/10.1002/1529-0131(199811)41:11<2004::AID-ART16>3.0.CO;2-Z
  15. Miyaura C, Inada M, Matsumoto C, Ohshiba T, Uozumi N, Shimizu T, Ito A. An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 197: 1303-1310, 2003 https://doi.org/10.1084/jem.20030015
  16. Miyazaki T, Katagiri H, Kanegae Y, Takayanagi H, Sawada Y, Yamamoto A, Pando MP, Asano T, Verma IM, Oda H, Nakamura K, Tanaka S. Reciprocal role of ERK and NF­kappaB pathways in survival and activation of osteoclasts. J Cell Biol 148: 333-342, 2000 https://doi.org/10.1083/jcb.148.2.333
  17. Motyckova G, Weilbaecher KN, Horstmann M, Rieman DJ, Fisher DZ, Fisher DE. Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family. Proc Natl Acad Sci U S A 98: 5798-5803, 2001 https://doi.org/10.1073/pnas.091479298
  18. Mozar A, Haren N, Chasseraud M, Louvet L, Maziere C, Wattel A, Mentaverri R, Morliere P, Kamel S, Brazier M, Maziere JC, Massy ZA. High extracellular inorganic phosphate concentration inhibits RANK-RANKL signaling in osteoclast-like cells. J Cell Physiol 215: 47-54, 2008 https://doi.org/10.1002/jcp.21283
  19. Oh SY, Aryal DK, Kim YG, Kim HG. Effects of R. Glutinosa and E. Senticosus on Postmenopausal Osteoporosis. Korean J Physiol Pharmacol 11: 121-127, 2007
  20. Reddy SV, Hundley JE, Windle JJ, Alcantara O, Linn R, Leach RJ, Boldt DH, Roodman GD. Characterization of the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. J Bone Miner Res 10: 601-606, 1995 https://doi.org/10.1002/jbmr.5650100413
  21. Rubnov S, Kashman Y, Rabinowitz R, Schlesinger M, Mechoulam R. Suppressors of cancer cell proliferation from Fig (Ficus carica) Resin: isolation and structure elucidation. J Nat Prod 64: 993-996, 2001 https://doi.org/10.1021/np000592z
  22. Serraclara A, Hawkins F, Pérez C, Domínguez E, Campillo JE, Torres MD. Hypoglycemic action of an oral fig-leaf decoction in type-I diabetic patients. Diabetes Res Clin Pract 39: 19-22, 1998 https://doi.org/10.1016/S0168-8227(97)00112-5
  23. Soh Y, Jeong KS, Lee IJ, Bae MA, Kim YC, Song BJ. Selective activation of the c-Jun N-terminal protein kinase pathway during 4-hydroxynonenal-induced apoptosis of PC12 cells. Mol Pharmacol 58: 534-541, 2000
  24. Soh Y, Shin MH, Lee JS, Jang JH, Kim OH, Kang H, Surh YJ. Oxidative DNA damage and glioma cell death induced by tetrahydropapaveroline. Mutat Res 544: 129-142, 2003 https://doi.org/10.1016/j.mrrev.2003.06.023
  25. Stern PH. Antiresorptive agents and osteoclast apoptosis. J Cell Biochem 101: 1087-1096, 2007 https://doi.org/10.1002/jcb.21311
  26. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 4: 638-649, 2003 https://doi.org/10.1038/nrg1122
  27. Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 20: 795-823, 2002 https://doi.org/10.1146/annurev.immunol.20.100301.064753
  28. Vaira S, Alhawagri M, Anwisye I, Kitaura H, Faccio R, Novack DV. RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. J Clin Invest 118: 2088-2097, 2008
  29. Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115: 282-290, 2005
  30. Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H, Choi Y. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 4: 1041-1049, 1999 https://doi.org/10.1016/S1097-2765(00)80232-4
  31. Wong BR, Josien R, Lee SY, Vologodskaia M, Steinman RM, Choi Y. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. J Biol Chem 273: 28355-28359, 1998 https://doi.org/10.1074/jbc.273.43.28355
  32. Yamashita T, Yao Z, Li F, Zhang Q, Badell IR, Schwarz EM, Takeshita S, Wagner EF, Noda M, Matsuo K, Xing L, Boyce BF. NF-kappaB p50 and p52 regulate receptor activator of NF- kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1. J Biol Chem 282: 18245-18253, 2007 https://doi.org/10.1074/jbc.M610701200
  33. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD, Nishikawa S. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345: 442-444, 1990 https://doi.org/10.1038/345442a0
  34. Zhou B, Cron RQ, Wu B, Genin A, Wang Z, Liu S, Robson P, Baldwin HS. Regulation of the murine Nfatc1 gene by NFATc2. J Biol Chem 277: 10704-10711, 2002 https://doi.org/10.1074/jbc.M107068200

Cited by

  1. The Efficacy of Shikonin on Cartilage Protection in a Mouse Model of Rheumatoid Arthritis vol.14, pp.4, 2010, https://doi.org/10.4196/kjpp.2010.14.4.199
  2. Ethyl Docosahexaenoate and Its Acidic Form Increase Bone Formation by Induction of Osteoblast Differentiation and Inhibition of Osteoclastogenesis vol.19, pp.1, 2011, https://doi.org/10.4062/biomolther.2011.19.1.070
  3. Phytochemical andin vitroscreening of someFicusandMorusspp. for hypolipidaemic and antioxidant activities andin vivoassessment ofFicus mysorensis(Roth) vol.26, pp.12, 2012, https://doi.org/10.1080/14786419.2010.545353
  4. Methanolic Extract of Ficus carica Linn. Leaves Exerts Antiangiogenesis Effects Based on the Rat Air Pouch Model of Inflammation vol.2015, pp.None, 2009, https://doi.org/10.1155/2015/760405
  5. Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract vol.13, pp.5, 2016, https://doi.org/10.3892/mmr.2016.5015