파골세포에 대한 커큐민의 효과
Effects of Curcumin on Osteoclasts
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI staining revealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.
Abstract
Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI staining revealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.
참고문헌 (26)
- Rodan, G.A., "Therapeutic approaches to bone diseases", Science, 289, pp.1508~1514 (2000)
- Boyle, W.J., "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2003)
- Teitelbaum, S.L., "Genetic regulation of osteoclast development and function", Nat Rev Genet, 3, pp.638~649 (2003)
- Takayanagi, H., "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems", Nat Rev Immunol, 7, pp.292~304 (2007)
- Thompson, C.B., "Apoptosis in the pathogenesis and treatment of disease", Science, 267, pp.1456~1462 (1995)
- Saudou, F., "Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions", Cell, 95, pp.55~66 (1998)
- Salvesen, G.S., "Caspases: intracellular signaling by proteolysis", Cell, 91, pp.443~446 (1997)
- Li, P., "Cytochrome c and dATP-dependent formation of Apaf-1", caspase-9 complex initiates an apoptotic protease cascade, 1997, pp.91, 479~489
- Lindsten, T., "The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues", Mol Cell, 6, pp.1389~1399 (2000)
- Jiang, X., "Cytochrome c-mediated apoptosis", Annu Rev Biochem, 73, pp.87~106 (2004)
- Strasser, A., "Apoptosis signaling", Annu Rev Biochem, 69, pp.217~245 (2000)
- Wang, X., "The expanding role of mitochondria in apoptosis", Genes Dev, 15, pp.2922~2933 (2001)
- Wang, Z.B., "Pathways to caspase activation", Cell Biol Int, 29, pp.489~496 (2007)
- Goel, A., "Curcumin as "Curecumin": From kitchen to clinic", Biochem Pharmacol, 75, pp.787~809 (2008)
- 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)
- Kwak, H.B., "Inhibition of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative", SCOH Biochem Pharmacol, 67, pp.1239~1248 (2004)
- Lee, S.E., "Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK", J Biol Chem, 276, pp.49343~49349 (2001)
- Vaananen, H.K., "The cell biology of osteoclast function", J Cell Sci, 113, pp.377~381 (2000)
- Tanaka, S., "Molecular mechanism of the life and death of the osteoclast", Ann N Y Acad Sci, 1068, pp.180~186 (2006)
- Glantschnig, H., "M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR", S6 kinase, 2003, pp.10, 1165~1177
- Akiyama, T., "Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim", EMBO J, 22, pp.6653~6664 (2003)
- Liu, W., "Receptor activator of NF-kappaB (RANK) cytoplasmic motif, 369PFQEP373, plays a predominant role in osteoclast survival in part by activating Akt", PKB and its downstream effector AFX, J Biol Chem, pp.2005, 280[DOI]
- Karsdal, M.A., "Calcitonin a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality", BioDrugs, 22(3), pp.137~144 (2008)
- Bond, M., "Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappaB", FEBS Lett, 435, pp.29~34 (1998)
- Kamolmatyakul, S., "IL-1alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappaB pathway", J Dent Res, 83, pp.791~796 (2004)
- Singh, S., "Activation of transcription factor NF-kappaB is suppressed by curcumin (diferuloylmethane)", J Biol Chem, 270, pp.24995~24995 (1995)