Browse > Article

Effects of Curcumin on Osteoclasts  

Kim, Jeong-Joong (Departments of Anatomy, College of Medicine, Wonkwang University)
Kim, Dong-Joo (Departments of Anatomy, College of Medicine, Wonkwang University)
Lee, Byung-Ki (Departments of Anatomy, College of Medicine, Wonkwang University)
Kim, Kwang-Jin (Departments of Anatomy, College of Medicine, Wonkwang University)
Lee, Myeung-Su (Departments of Internal Medicine, College of Medicine, Wonkwang University)
Lee, Jae-Hoon (Departments of Internal Medicine, College of Medicine, Wonkwang University)
Kim, Hun-Soo (Departments of Pathology, College of Medicine, Wonkwang University)
Lee, Chang-Hoon (Departments of Internal Medicine, College of Medicine, Wonkwang University)
Byun, Seung-Jae (Departments of Neurosurgery, College of Medicine, Wonkwang University)
Jang, Sung-Jo (Departments of Reconstructive Surgery, College of Medicine, Wonkwang University)
Song, Jeong-Hoon (Departments of Plastic Surgery, College of Medicine, Wonkwang University)
Oh, Jae-Min (Departments of Anatomy, College of Medicine, Wonkwang University)
Lee, Jun-Seok (Departments of Obstetrics and Gynecology, College of Medicine, Wonkwang University)
Kim, Kwang-Mee (Department of Anatomy, College of Medicine, Wonkwang University)
Chun, Churl-Hong (Department of Orthopaedic, College of Medicine, Wonkwang University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.22, no.6, 2008 , pp. 1566-1571 More about this Journal
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 stainingrevealed 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.
Keywords
bone; osteoclast; curcumin;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Kwak, H.B., Lee, S.W., Li, Y.J., Kim, Y.A., Han, S.Y., Jhon, G.J. et al. Inhibition of osteoclast differentiation and bone resorption by a novel lysophosphatidylcholine derivative. SCOH Biochem Pharmacol 67: 1239-1248, 2004.   DOI   ScienceOn
2 Bond, M., Fabunmi, R.P., Baker, A.H. and Newby, A.C. Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappaB. FEBS Lett 435: 29-34, 1998.   DOI   ScienceOn
3 Singh, S., Aggarwal, B.B. Activation of transcription factor NF-kappaB is suppressed by curcumin (diferuloylmethane). J Biol Chem 270: 24995, 1995.   DOI   ScienceOn
4 Karsdal, M.A., Henriksen, K., Arnold, M., Christiansen, C. 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):137-144, 2008.   DOI   ScienceOn
5 Salvesen, G.S. and Dixit, V.M. Caspases: intracellular signaling by proteolysis. Cell 91: 443-446, 1997.   DOI   ScienceOn
6 Glantschnig, H., Fisher, J.E., Wesolowski, G., Rodan, G.A., Reszka, A.A. M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell death Differ 10: 1165-1177, 2003.   DOI   ScienceOn
7 Lindsten, T., Ross, A.J., King, A., Zong, W.X., Rathmell, J.C., Shiels, H.A. et al. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6: 1389-1399, 2000.   DOI   ScienceOn
8 Wang, X. The expanding role of mitochondria in apoptosis. Genes Dev 15: 2922-2933, 2001.
9 Wang, Z.B., Liu, Y.Q. and Cui, Y.F. Pathways to caspase activation. Cell Biol Int 29: 489-496, 2007.
10 Boyle, W.J., Simonet, W.S., Lacey, D.L. Osteoclast differentiation and activation. Nature 423: 337-342, 2003.   DOI   ScienceOn
11 Kamolmatyakul, S., Chen, W., Yang, S., Abe, Y., Moroi, R., Ashique, A.M. and Li YP: IL-1alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappaB pathway. J Dent Res 83: 791-796, 2004.   DOI   ScienceOn
12 Takayanagi, H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7: 292-304, 2007.   DOI   ScienceOn
13 Vaananen, H.K., Zhao, H., Mulari, M. and Halleen, J.M. The cell biology of osteoclast function. J Cell Sci 113: 377-381, 2000.
14 Bharti, A.C., Takada, Y., Aggarwal, B.B. Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol 172: 5940-5947, 2004.   DOI
15 Tanaka, S., Miyazaki, T., Fukuda, A., Akiyama, T., Kadono, Y., Wakeyama, H., Kono, S., Hoshikawa, S., Nakamura, M., Ohshima, Y., Hikita, A., Nakamura, I. and Nakamura, K. Molecular mechanism of the life and death of the osteoclast. Ann N Y Acad Sci 1068: 180-186, 2006.   DOI
16 Saudou, F., Finkbeiner, S., Devys, D., Greenberg, M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95: 55-66, 1998.   DOI   ScienceOn
17 Liu, W., Wang, S., Wei, S., Sun, L., Feng, X. 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/FOXO4. J Biol Chem 280: 43064-43072, 2005.   DOI   ScienceOn
18 Strasser, A., O'Connor, L. and Dixit, V.M. Apoptosis signaling. Annu Rev Biochem 69: 217-245, 2000.   DOI   ScienceOn
19 Akiyama, T., Bouillet, P., Miyazaki, T., Kadono, Y., Chikuda, H., Chung, U.I., Fukuda, A., Hikita, A., Seto, H., Okada, T., Inaba, T., Sanjay, A., Baron, R., Kawaguchi, H., Oda, H., Nakamura, K., Strasser, A. and Tanaka, S. Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim. EMBO J 22: 6653-6664, 2003.   DOI   ScienceOn
20 Rodan, G.A., Martin, T.J. Therapeutic approaches to bone diseases. Science 289: 1508-1514, 2000.   DOI
21 Jiang, X., Wang, X. Cytochrome c-mediated apoptosis. Annu Rev Biochem 73: 87-106, 2004.   DOI   ScienceOn
22 Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S. and Wang, X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489, 1997.   DOI   ScienceOn
23 Teitelbaum, S.L., Ross, F.P. Genetic regulation of osteoclast development and function. Nat Rev Genet 3: 638-649, 2003.
24 Thompson, C.B. Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456-1462, 1995.   DOI
25 Goel, A., Kunnumakkara, A.B., Aggarwal, B.B. Curcumin as "Curecumin": From kitchen to clinic. Biochem Pharmacol 75: 787-809, 2008.   DOI   ScienceOn
26 Lee, S.E., Chung, W.J., Kwak, H.B., Chung, C.H., Kwack, K.B., Lee, Z.H. and Kim, H.H. Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem 276: 49343-49349, 2001.   DOI   ScienceOn