Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways

Shang,Wei; Zhao,Ling‑Jie; Dong,Xiao‑Lei; Zhao,Zhi‑Ming; Li,Jing; Zhang,Bei‑Bei; Cai,Hui

doi:10.3892/mmr.2016.5674

Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways

Authors:
- Wei Shang
- Ling‑Jie Zhao
- Xiao‑Lei Dong
- Zhi‑Ming Zhao
- Jing Li
- Bei‑Bei Zhang
- Hui Cai
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Affiliations: The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China, Department of Integrated Traditional Chinese and Western Medicine, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China
Published online on: August 25, 2016 https://doi.org/10.3892/mmr.2016.5674
Pages: 3620-3626
Copyright: © Shang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate‑resistant acid phosphatase‑positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T‑score (r=‑0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC‑derived osteoclasts treated with curcumin were measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal‑regulated kinases 1 and 2, p38 and c‑Jun N‑terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c‑Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen‑activated protein kinase/RANK/c‑Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA.

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1	Wendling D, Abbas W, Godfrin-Valnet M, Kumar A, Guillot X, Khan KA, Vidon C, Coquard L, Toussirot E, Prati C and Herbein G: Dysregulated serum IL-23 and SIRT1 activity in peripheral blood mononuclear cells of patients with rheumatoid arthritis. PloS One. 10:e01199812015. View Article : Google Scholar : PubMed/NCBI
2	Han M, Sung YK, Cho SK, Kim D, Won S, Choi CB, Bang SY, Cha HS, Choe JY, Chung WT, et al: Factors associated with the use of complementary and alternative medicine for Korean patients with rheumatoid arthritis. J Rheumatol. 42:2075–2081. 2015. View Article : Google Scholar : PubMed/NCBI
3	Jung SM, Kim KW, Yang CW, Park SH and Ju JH: Cytokine-mediated bone destruction in rheumatoid arthritis. J Immunol Res. 2014:2636252014. View Article : Google Scholar : PubMed/NCBI
4	Jules J, Wang S, Shi Z, Liu J, Wei S and Feng X: The IVVY motif and tumor necrosis factor receptor associated factor (TRAF) sites in the cytoplasmic domain of the receptor activator of nuclear factor κB (RANK) cooperate to induce osteoclastogenesis. J Biol Chem. 290:23738–23750. 2015. View Article : Google Scholar : PubMed/NCBI
5	Kong X, Yang Y, Wu W, Wan H, Li X, Zhong M, Su X, Jia S and Lin N: Triterpenoid Saponin W3 from Anemone flaccida suppresses osteoclast differentiation through inhibiting activation of MAPKs and NF-κB pathways. Int J Biol Sci. 11:1204–1214. 2015. View Article : Google Scholar :
6	Schulze-Koops H, Davis LS, Kavanaugh AF and Lipsky PE: Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation. Arthritis Rheum. 40:639–647. 1997. View Article : Google Scholar : PubMed/NCBI
7	Ikić M, Jajić Z, Lazić E, Ivčević S, Grubišić F, Marušić A, Kovačić N and Grčević D: Association of systemic and intra-articular osteoclastogenic potential, proinflammatory mediators and disease activity with the form of inflammatory arthritis. Int Orthop. 38:183–192. 2014. View Article : Google Scholar
8	Yang Y, Wu X, Wei Z, Dou Y, Zhao D, Wang T, Bian D, Tong B, Xia Y, Xia Y and Dai Y: Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine. Pharmacol Res. 95–96:71–81. 2015. View Article : Google Scholar
9	Kloesch B, Becker T, Dietersdorfer E, Kiener H and Steiner G: Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes. Int Immunopharmacol. 15:400–405. 2013. View Article : Google Scholar : PubMed/NCBI
10	Huang G, Xu Z, Huang Y, Duan X, Gong W, Zhang Y, Fan J and He F: Curcumin protects against collagen-induced arthritis via suppression of BAFF production. J Clin Immunol. 33:550–557. 2013. View Article : Google Scholar
11	Chandran B and Goel A: A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 26:1719–1725. 2012. View Article : Google Scholar : PubMed/NCBI
12	Niu X, Lu C, Xiao C, Zhang Z, Jiang M, He D, Bian Y, Zhang G, Bian Z and Lu A: The shared crosstalk of multiple pathways involved in the inflammation between rheumatoid arthritis and coronary artery disease based on a digital gene expression profile. PloS One. 9:e1136592014. View Article : Google Scholar : PubMed/NCBI
13	Buhrmann C, Mobasheri A, Matis U and Shakibaei M: Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment. Arthritis Res Ther. 12:R1272010. View Article : Google Scholar
14	Shakibaei M, Mobasheri A and Buhrmann C: Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro. Genes Nutr. 6:171–179. 2011. View Article : Google Scholar : PubMed/NCBI
15	von Metzler I, Krebbel H, Kuckelkorn U, Heider U, Jakob C, Kaiser M, Fleissner C, Terpos E and Sezer O: Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated I kappaB kinase. J Cancer Res Clin Oncol. 135:173–179. 2009. View Article : Google Scholar
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
17	Ravindran J, Cavill C, Balakrishnan C, Jones SM, Korendowych E and McHugh NJ: A modified Sharp score demonstrates disease progression in established psoriatic arthritis. Arthritis Care Res (Hoboken). 62:86–91. 2010. View Article : Google Scholar
18	Chen P, Miller PD, Binkley NC, Kendler DL, Wong M and Krohn K: Use of lowest single lumbar spine vertebra bone mineral density T-score and other T-score approaches for diagnosing osteoporosis and relationships with vertebral fracture status. J Clin Densitom. 11:525–531. 2008. View Article : Google Scholar : PubMed/NCBI
19	Kim JY, Min JY, Baek JM, Ahn SJ, Jun HY, Yoon KH, Choi MK, Lee MS and Oh J: CTRP3 acts as a negative regulator of osteoclastogenesis through AMPK-c-Fos-NFATc1 signaling in vitro and RANKL-induced calvarial bone destruction in vivo. Bone. 79:242–251. 2015. View Article : Google Scholar : PubMed/NCBI
20	Shi C and Pamer EG: Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 11:762–774. 2011. View Article : Google Scholar : PubMed/NCBI
21	McInnes IB and Schett G: The pathogenesis of rheumatoid arthritis. N Engl J Med. 365:2205–2219. 2011. View Article : Google Scholar : PubMed/NCBI
22	Pathak JL, Bravenboer N, Verschueren P, Lems WF, Luyten FP, Klein-Nulend J and Bakker AD: Inflammatory factors in the circulation of patients with active rheumatoid arthritis stimulate osteoclastogenesis via endogenous cytokine production by osteoblasts. Osteoporos Int. 25:2453–2463. 2014. View Article : Google Scholar : PubMed/NCBI
23	Izawa T, Mori H, Shinohara T, Mino-Oka A, Hutami IR, Iwasa A and Tanaka E: Rebamipide attenuates mandibular condylar degeneration in a murine model of TMJ-OA by mediating a chondroprotective effect and by downregulating RANKL-mediated osteoclastogenesis. PloS One. 11:e01541072016. View Article : Google Scholar : PubMed/NCBI
24	Adamopoulos IE, Chao CC, Geissler R, Laface D, Blumenschein W, Iwakura Y, McClanahan T and Bowman EP: Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors. Arthritis Res Ther. 12:R292010. View Article : Google Scholar : PubMed/NCBI
25	Gravallese EM, Harada Y, Wang JT, Gorn AH, Thornhill TS and Goldring SR: Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol. 152:943–951. 1998.PubMed/NCBI
26	Lee EG, Yun HJ, Lee SI and Yoo WH: Ethyl acetate fraction from Cudrania tricuspidata inhibits IL-1beta-stimulated osteoclast differentiation through downregulation of MAPKs, c-Fos and NFATc1. Korean J Intern Med. 25:93–100. 2010. View Article : Google Scholar : PubMed/NCBI
27	Lee ZH and Kim HH: Signal transduction by receptor activator of nuclear factor kappaB in osteoclasts. Biochem Biophys Res Commun. 305:211–214. 2003. View Article : Google Scholar : PubMed/NCBI
28	Takayanagi H: Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med (Berl). 83:170–179. 2005. View Article : Google Scholar