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파골세포의 분화에 커규민의 억제 작용기전

Inhibitory Mechanism of Curcumin in Osteoclast Differentiation

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초록

Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated I-κB degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

Abstract

Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated I-κB degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

참고문헌 (20)

  1. Suda, T, "Modulation of osteoclast differentiation and function and ligand families", Endocr. Rev, 20, pp.345~357 (1999)
  2. Boyle, W.J, "Osteoclast differentiation and activation", Nature, 통권 : 423, pp.337~342 (2003)
  3. Teitelbaum, S.L, "Genetic regulation of osteoclast development and function", Nat. Rev. Genet, 4, pp.638~649 (2003)
  4. Takayanagi, H, "Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts", Dev. Cell, 3, pp.889~901 (2002)
  5. Koga, T, "Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis", Nature, 428, pp.758~763 (2004)
  6. Takayanagi, H, "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems", Nat. Rev. Immunol, 7, pp.292~304 (2007)
  7. Shinohara, M, "Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals", Cell, 132, pp.794~806 (2008)
  8. Lee, J, "Id helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation", Blood, 107, pp.2686~2693 (2006)
  9. Kim, K, "MafB negatively regulates RANKL-mediated osteoclast differentiation", Blood, 109, pp.3253~3259 (2007)
  10. Goel, A, "Kunnumakkara, A.B., Aggarwal, B.B. Curcumin as "Curecumin": From kitchen to clinic", Biochem. Pharmacol, 75, pp.787~809 (2008)
  11. Shishodia, S, "Modulation of transcription factors by curcumin", Adv. Exp. Med. Biol, 595, pp.127~148 (2007)
  12. Bharti, A.C, "Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis", J. Immunol, 172, pp.5940~5947 (2004)
  13. Karsenty, G, "Reaching a genetic and molecular understanding of skeletal development", Dev. Cell, 2, pp.389~406 (2002)
  14. Partington, G.A, "Mitf-PU. 1 interactions with the tartrate-resistant acid phosphatase gene promoter during osteoclast differentiation", Bone, 34, pp.237~245 (2004)
  15. Matsumoto, M, "Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL)", J. Biol. Chem, 275, pp.31155~31161 (2000)
  16. Jimi, E, "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function", J. Immunol, 163, pp.434~442 (1999)
  17. Jimi, E, "Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo", Nat. Med, 10, pp.617~624 (2004)
  18. Isotsova, V, "Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2", Nat. Med, 3, pp.1285~1289 (1997)
  19. Lin, L, "Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome", Cell, 92, pp.819~828 (1998)
  20. Fleischmann, A, "Fra-1 replaces c-Fos-dependent functions in mice", Genes Dev, 14, pp.2695~2700 (2000)

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