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Curcumin Inhibits Osteoclastogenesis by Decreasing Receptor Activator of Nuclear Factor-κB Ligand (RANKL) in Bone Marrow Stromal Cells  

Oh, Sora (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Kyung, Tae-Wook (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Choi, Hye-Seon (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Abstract
Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant and anti-inflammatory activities. Accumulating evidence points to a biochemical link between increased oxidative stress and reduced bone density. Osteoclast formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to curcumin led to dose-dependent suppression of osteoclastogenesis in the co-culture system, and to reduced expression of RANKL in $IL-1{\alpha}$-stimulated BMSCs. Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin, whereas the addition of prostaglandin $E_2$ ($PGE_2$) did not. The decreased osteoclastogenesis induced by curcumin may reduce bone loss and be of potential benefit in preventing and/or attenuating osteoporosis.
Keywords
bone; bone marrow stromal cells; curcumin; osteoclastogenesis; receptor activator of nuclear factor-${\kappa}B$ ligand;
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1 Wong, B.R., Josien, R., Lee, S.Y., Vologodskaia, M., Steinman, R.M., and Choi, Y. (1998). The TRAF family of signal transducers mediates nuclear factor-${\kappa}B$ activation by the TRANCE receptor. J. Biol. Chem. 273, 28355-28359   DOI   ScienceOn
2 Bai, X., Lu, D., Liu, A., Zhang, Z., Li, X., Zou, Z., Zeng, W., Cheng, B., and Luo, S. (2005). Reactive oxygen species stimulates receptor activator of NF-${\kappa}B$ ligand expression in osteoblast. J. Biol. Chem. 280, 17497-17506   DOI   ScienceOn
3 Bharti, A.C., Takada, Y., and Aggarwal, B.B. (2004). Curcumin(diferuloylmethane). inhibits receptor for activation of nuclear factor-${\kappa}B$ ligand induced NF-${\kappa}B$ activation in osteoclast precursors and suppress osteoclastogenesis. J. Immunol. 172, 5940-5947
4 Eghbali-Fatourechi, G., Khosla, S., Sanyal, A., Boyle, W.J., Lacey, D.L., and Riggs, B.L. (2003). Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J. Clin. Invest. 111, 1221-1230   DOI
5 Fraser, J.H., Helfrich, M.H., Wallace, H.M., and Ralston, S.H. (1996). Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae. Bone 19, 223-226   DOI   ScienceOn
6 Lee, S.Y., Reichlin, A., Santana, A., Sokol, K.A., Nussenzweig, M.C., and Choi, Y. (1997). TRAF2 is essential for JNK but not NF-${\kappa}B$ activation and regulates lymphocytes proliferation and survival. Immunity 7, 703-713   DOI   ScienceOn
7 Shin, H.H., Kim, S.J., Kang, S.Y., Lee, D.S., and Choi, H.S. (2006a). Soluble glucocorticoid induced tumor necrosis factor receptor stimulates osteoclastogenesis by down-regulation of osteoprotegerin in bone marrow stromal cells. Bone 39, 716-723   DOI   ScienceOn
8 Suda, K., Udagawa, N., Sato, N., Takami, M., Itoh, K., Woo, J.-T., Takahashi, N., and Nagai, K. (2004). Suppression of osteoprotegerin expression by prostaglandin $E_2$ is crucially involved in lipopolysaccharide-induced osteoclast formation. J. Immunol. 172, 2504-2510   DOI
9 Shin, H.H., Lee, J.E., Lee, E.A., Kwon, B.S., and Choi, H.S. (2006b). Enhanced osteoclastogenesis in 4-1BB-deficient mice caused by reduced interleukin-10. J. Bone Miner. Res. 21, 1907-1912   DOI   ScienceOn
10 Lean, J.M., Davies, J.T., Fuller, K., Jagger, C.J., Kirstein, B., Partington, G.A., Urry, Z.L., and Chamber, T.J. (2003). A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J. Clin. Invest. 112, 915-923   DOI
11 Brandstrom, H., Jonsson, K.B., Ohlsson, C., Vidal, O., Ljunghall, S., and Ljunggren, O. (1998). Regulation of osteoprotegerin mRNA levels by prostaglandin $E_2$ in human bone marrow stroma cells. Biochem. Biophys. Res. Commun. 247, 338-341   DOI   ScienceOn
12 Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998). Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA 95, 3597-3602
13 Lee, S.K., and Lorenzo, J.A. (1999). Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinol. 140, 3552-3561   DOI   ScienceOn
14 Tai, H., Miyaura, C., Pilbeam, C.C., Tamura, T., Ohsugi, Y., Koishihara, Y., Kubodera, N., Kawaguchi, H., Raisz, L.G., and Suda, T. (1997). Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation. Endocrinology 138, 2372-2379   DOI   ScienceOn
15 Kluth, D., Banning, A., Paur, I., Blomhoff, R., and Brigelius-Flohe, R. (2007). Modulation of pregnane X receptor and electrophile responsive element-mediated gene expression by dietary polyphenolic compounds. Free Radic. Biol. Med. 42, 315-325   DOI   ScienceOn
16 Aggarwal, B.B., Kumar, A., and Bharti, A.C. (2003). Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23, 363-398
17 Ozaki, K., Kawata, Y., Amano, S., and Hanazawa, S. (2000). Stimulatory effect of curcumin on osteoclasst apoptosis. Biochem. Pharmacol. 59, 1577-1581   DOI   ScienceOn
18 Kong, Y.Y., Yoshida, H., Sarosi, I., Tan, H.L., Timms, E., Capparelli, C., Morony, S., Olivereira-dos-Santos, A.J., Van, G., Itie, A., et al. (1997). OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315-323   DOI
19 Uchida, K. (2008). A lipid-derived endogenous inducer of COX-2: a bridge between inflammation and oxidative stress. Mol. Cell 25, 347-351
20 Mody, M., Parhami, F., Saraflan, T.A., and Demer, L.L. (2001). Oxidative stress modulates osteoblast differentiation of vascular and bone cells. Free Radic. Biol. Med. 31, 509-519   DOI   ScienceOn
21 Darnay, B.G., Ni, J., Moore, P.A., and Aggarwal, B.B. (1999). Activation of nuclear factor-${\kappa}B$ by RANK requires tumor necrosis factor receptor-associated factor (TRAF). 6 and NF-${\kappa}B$ inducing kinase: identification of a novel TRAF6 interaction motif. J. Biol. Chem. 274, 7724-7731   DOI   ScienceOn
22 Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M.T., and Martin, T.J. (1999). Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrinol. Rev. 20, 345-357   DOI   ScienceOn
23 Cheng, A.L., Hsu, C.H., Lin, J.K., Hsu, M.M., Ho, Y.F., Shen, T.S., Ko, J.Y., Lin, J.T., Lin, B.R., Ming-Shiang, W., et al. (2001). Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 21, 2895-2900
24 Lin, J.K. (2007). Molecular targets of curcumin. Adv. Exp. Med. Biol. 596, 227-243
25 Nishiumi, S., Yoshida, K., and Ashida, H. (2007). Curcumin suppresses the transformation of an aryl hydrocarbon receptor through its phosphorylation. Arch. Biochem. Biophys. 466, 267-273   DOI   ScienceOn
26 Tropel, P., Noel, D., Platet, N., Legrand, P., Benabid, A.L., and Berger, F. (2004). Isolation and characterization of mesenchymal stem cells from adult mouse bone marrow. Exp. Cell Res. 295, 395-406   DOI   ScienceOn
27 Gradisar, H., Keber, M.M., Pristovsek, P., and Jerala, R. (2007). MD-2 as the target of curcumin in the inhibition of response to LPS. J. Leukoc. Biol. 82, 968-974   DOI   ScienceOn