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Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats

Abstract

Simon extracts are vitamin K1-rich food materials extracted from the leaves of the Simon sweet potato. Although vitamin K is known to stimulate bone formation, we postulated that Simon extracts also contain unknown biological compounds having the ability to regulate bone resorption. Here we prepared the vitamin K-free fraction from the Simon extracts and investigated the ability of this fraction on the differentiation of osteoclasts. A remarkable inhibitory effect of osteoclastogenesis was observed when osteoclast precursors were treated with this fraction in rat bone marrow culture systems as well as in a pure differentiation system using murine osteoclast precursor cell line. The vitamin K-free Simon extracts markedly suppressed severe bone destruction mediated by abundant osteoclasts associated with adjuvant-induced arthritis in rats. High performance liquid chromatography (HPLC) analysis revealed that the vitamin K-free Simon extracts contained three types of low molecular weight inhibitors for osteoclastogenesis; caffeic acid, chlorogenic acids and isochlorogenic acids. Among these substances, caffeic acid showed the most powerful inhibitory effects on osteoclastogenesis. Caffeic acid significantly suppressed expression of NFATc1, a key transcription factor for the induction of osteoclastogenesis. Our current study enlightened a high utility of the Simon extracts and their chemical components as effective regulators for bone resorption accompanied with inflammation and metabolic bone diseases.

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References

  1. Abramson SB, Amin A (2002) Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology 41:972–980

  2. Andreakos ET, Foxwell BM, Brennan FM, Maini RN, Feldman M (2002) Cytokines and anti-cytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev 13:299–313

  3. Borrelli F, Maffia P, Pinto L, Ianaro A, Russo A, Capasso F, Ialenti A (2002) Phytochemical compounds involved in the anti-inflammatory effect of propolis extract. Fitoterapia 73(suppl. 1):S53–S63

  4. Chen YJ, Shiao MS, Wang SY (2001) The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cell. Anticancer Drugs 12:143–149

  5. Cimaz R (2002) Osteoporosis in childhood rheumatic diseases: prevention and therapy. Best Pract Res Clin Rheumatol 16:397–409

  6. Fitzpatrick LR, Wang J, Le T (2001) Caffeic acid phenethyl ester, an inhibitor of nuclear factor-κB, attenuates bacterial peptidoglycan polysaccharide-induced colitis in rats. J Pharmacol Exp Ther 299:915–920

  7. Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A (2003) Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr 133:1853–1859

  8. Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF (1994) c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266:443–448

  9. Heer M (2002) Nutritional interventions related to bone turnover in European space mission and simulation models. J Nutr 18:853–856

  10. Hirayama T, Danks L, Sabokbar A, Athanasou NA (2002) Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis. Rheumatology 41:1232–1239

  11. Ikeda F, Nishimura R, Matsubara T, Tanaka S, Inoue J, Reddy SV, Hata K, Yamashita K, Hiraga T, Watanabe T, Kukita T, Yoshioka K, Rao A, Yoneda T (2004) Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J Clin Invest 114:475–484

  12. Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R (1997) Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med 3:1285–1289

  13. Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T (2002) Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem 277:41147–41156

  14. Ishihara K, Hirano T (2002) IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 13:357–368

  15. Jimi E, Nakamura I, Ikebe T, Akiyama S, Takahashi N, Suda T (1998) Activation of NF-κB is involved in the survival of osteoclasts promoted by interleukin-1. J Biol Chem 273:8799–8805

  16. Jue DM, Jeon KI, Jeong JY (1999) Nuclear factor κB (NF-κB) pathway as a therapeutic target in rheumatoid arthritis. J Korean Med Sci 14:231–238

  17. Khosla S and Kleerekoper M (1999) Biochemical markers of bone turnover. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 128–133

  18. Krol W, Scheller S, Czuba Z, Matsuno T, Zydowicz G, Shani J, Mos M (1996) Inhibition of neutrophils’ chemiluminescence by ethanol extract of propolis (EEP) and its phenolic components. J Ethnopharma 55:19–25

  19. Kukita A, Kukita T, Hata K, Kurisu K, Kohashi O (1993a) Heat-treated osteoblastic cell (ROS17/2.8)-conditioned medium induces the formation of osteoclast-like cells. Bone Miner 23:113–127

  20. Kukita A, Kukita T, Shin JH, Kohashi O (1993b) Induction of mononuclear precursor cells with osteoclastic phenotypes in a rat bone marrow culture system depleted of stromal cells. Biochem Biophys Res Commun 196:1383–1389

  21. Kukita A, Kukita T, Ouchida M, Maeda H, Yatsuki H, Kohashi O (1999) Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis. Blood 94:1987–1997

  22. Kuratani T, Nagata K, Kukita T, Hotokebuchi T, Nakashima A, Iijima T (1998) Induction of abundant osteoclast-like multinucleated giant cells in adjuvant arthritic rats with accompanying disordered high bone turnover. Histol Histopathol 13:751–759

  23. Makarov SS (2001) NF-κB in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res 3:200–206

  24. Moller HJ (1998) Connective tissue markers of rheumatoid arthritis. Scand J Clin Lab Invest 58:269–278

  25. Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggareal BB (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-κB. Proc Natl Acad Sci USA 93: 9090–9095

  26. Orban Z, Mitsiades N, Burke TR Jr, Tsokos M, Chrousos GP (2000) Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation. Neuroimmunomodulation 7:99–105

  27. Rodan GA, Martin TJ (2000) Therapeutic approaches to bone diseases. Science 289:1508–1514

  28. Romas E, Gillespie MT, Martin TJ (2002) Involvement of receptor activator of NF-κB ligand and tumor necrosis factor-α in bone destruction in rheumatoid arthritis. Bone 30:340–346

  29. Shankar VS, Pazianas M, Huang CL, Simon B, Adebanjo OA, Zaidi M (1995) Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release. Am J Physiol Renal Physiol 268: 447–454

  30. Tabb MM, Sun A, Zhou C, Grun F, Errandi J, Romero K, Pham H, Inoue S, Mallick S, Lin M (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem 278:43919–43927

  31. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3:889–901

  32. Teitelbaum SL, Ross FP (2003) Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638–649

  33. Tezuka K, Tezuka Y, Maejima A, Sato T, Nemoto K, Kamioka H, Hakeda Y, Kumegawa M (1994) Molecular cloning of a possible cysteine proteinase predominantly express in osteoclasts. J Biol Chem 269:1106–1109

  34. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M, Maki R, Teitelbaum SL (1997) Osteopetrosis in mice lacking haematopoietic transcription factor PU. 1. Nature 386:81–84

  35. Toraldo G, Roggia C, Qian WP, Pacifici R, Weitzmann M.N (2003) IL-7 induce bone loss in vivo by induction of receptor activator of nuclear factorκ B ligand and tumor necrosis factor αfrom T cells. Proc Natl Acad Sci USA 100:125–130

  36. Watanabe T, Kukita T, Kukita A, Wata N, Toh K, Nagata K, Nomiyama H, Iijima T (2004) Direct stimulation of osteoclastogenesis by MIP-1α: evidence obtained from studies using RAW 264 cell clone highly responsive to RANKL. J Endocrinol 180:193–201

  37. Zaidi M, Moonga BS, Adebanjo OA (1999) Novel mechanism of calcium handling by osteoclast: a review-hypothesis. Proc Assoc Am Physicians 111:319–327

  38. Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL (2003) Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 18:599–609

  39. Zhao H P, Shuto T, Hirata G, Iwamoto Y (2000) Aminobisphosphonate (YM175) inhibits bone destruction in rat adjuvant arthritis. J Orthop Sci 5:397–403

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Acknowledgements

We thank Dr. Go Hirata of Department of Orthopedic Surgery, Faculty of Medical Science, Kyushu University for kind suggestions. This work was supported in part by a Grant for Scientific Research from the Japanese Ministry of Education, Science, and Culture (project 14571738). The authors have no conflicting financial interests.

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Correspondence to Toshio Kukita.

Additional information

Quan Yong Tang is on leave from Hebei Medical University of China

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Tang, Q.Y., Kukita, T., Ushijima, Y. et al. Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats. Histochem Cell Biol 125, 215–225 (2006). https://doi.org/10.1007/s00418-005-0062-4

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Keywords

  • Simon extracts
  • Osteoclastogenesis
  • Adjuvant-induced arthritis
  • Caffeic acid
  • Cathepsin K
  • Food materials
  • NFATc1