Resveratrol reduces the progression of titanium particle‑induced osteolysis via the Wnt/β‑catenin signaling pathway <em>in vivo</em> and <em>in vitro</em>

Chen,Xi; Sun,Shouxuan; Geng,Tianxiang; Fan,Xin; Zhang,Shifeng; Zhao,Sijia; Geng,Yi; Jin,Qunhua

doi:10.3892/etm.2021.10553

Resveratrol reduces the progression of titanium particle‑induced osteolysis via the Wnt/β‑catenin signaling pathway in vivo and in vitro

Authors:
- Xi Chen
- Shouxuan Sun
- Tianxiang Geng
- Xin Fan
- Shifeng Zhang
- Sijia Zhao
- Yi Geng
- Qunhua Jin
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Affiliations: Department of Orthopedic Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, P.R. China
Published online on: August 4, 2021 https://doi.org/10.3892/etm.2021.10553
Article Number: 1119
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As an activator of sirtuin 1, resveratrol has become an extensively reviewed anti‑inflammatory and anti‑aging drug in recent years, and it has been widely studied for the treatment of energy control and endocrine diseases. The present study attempted to characterize the role of resveratrol in osteolysis induced by titanium (Ti) alloy particles and Ti pins in vitro and in vivo. In vitro, bone marrow mesenchymal stem cells were cultured with Ti alloy particles to simulate osteolysis. Cell viability and the expression levels of proteins associated with osteogenesis and the Wnt/β‑catenin signaling pathway, including Runt‑related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, β‑catenin, lymphoid enhancer‑binding factor 1 and transcription factor 4, were increased following treatment with resveratrol after 21 days of osteogenic differentiation. In vivo, a Ti pin model in C57BL/6J mice was used to study the anti‑osteolysis effect of resveratrol on the peri‑prosthetic bone. The pulling force of the Ti alloy pin was increased in a dose‑dependent manner in the resveratrol groups compared with the control group. Furthermore, the results of micro‑CT scanning revealed that the bone volume and the bone surface/volume ratio in the periprosthetic tissue were increased in the resveratrol‑treated groups, particularly in the high‑dose resveratrol group. In addition, immunohistochemistry demonstrated that Runx2 expression was upregulated in the high‑dose resveratrol group. In conclusion, the results of the present study indicated that resveratrol may inhibit Ti particle‑induced osteolysis via activation of the Wnt/β‑catenin signaling pathway in vitro and in vivo.

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1	Wang ML, Sharkey PF and Tuan RS: Particle bioreactivity and wear-mediated osteolysis. J Arthroplasty. 19:1028–1038. 2004.PubMed/NCBI View Article : Google Scholar
2	Lee SS, Sharma AR, Choi BS, Jung JS, Chang JD, Park S, Salvati EA, Purdue EP, Song DK and Nam S: The effect of TNFa secreted from macrophages activated by titanium particles on osteogenic activity regulated by WNT/BMP signaling in osteoprogenitor cells. Biomaterials. 33:4251–4263. 2012.PubMed/NCBI View Article : Google Scholar
3	Yang H, Xu Y, Zhu M, Gu Y, Zhang W, Shao H, Wang Y, Ping Z, Hu X, Wang L and Geng D: Inhibition of titanium-particle-induced inflammatory osteolysis after local administration of dopamine and suppression of osteoclastogenesis via D2-like receptor signaling pathway. Biomaterials. 80:1–10. 2016.PubMed/NCBI View Article : Google Scholar
4	Rao AJ, Gibon E, Ma T, Yao Z, Smith RL and Goodman SB: Revision joint replacement, wear particles, and macrophage polarization. Acta Biomater. 8:2815–2823. 2012.PubMed/NCBI View Article : Google Scholar
5	Vermes C, Chandrasekaran R, Jacobs JJ, Galante JO, Roebuck KA and Glant TT: The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts. J Bone Joint Surg Am. 83:201–211. 2001.PubMed/NCBI View Article : Google Scholar
6	Liu X, Zhu S, Cui J, Shao H, Zhang W, Yang H, Xu Y, Geng D and Yu L: Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo. Acta Biomaterialia. 10:4912–4918. 2014.PubMed/NCBI View Article : Google Scholar
7	Guo H, Zhang J, Hao S and Jin Q: Adenovirus-mediated small interfering RNA targeting tumor necrosis factor-α inhibits titanium particle-induced osteoclastogenesis and bone resorption. Int J Mol Med. 32:296–306. 2013.PubMed/NCBI View Article : Google Scholar
8	Squillaro T, Peluso G and Galderisi U: Clinical trials with mesenchymal stem cells: An update. Cell Transplant. 25:829–848. 2016.PubMed/NCBI View Article : Google Scholar
9	Reginster JY, Brandi ML, Cannata-Andia J, Cooper C, Cortet B, Feron JM, Genant H, Palacios S, Ringe JD and Rizzoli R: The position of strontium ranelate in today's management of osteoporosis. Osteoporos Int. 26:1667–1671. 2015.PubMed/NCBI View Article : Google Scholar
10	Karakan NC, Akpinar A, Göze F and Poyraz Ö: Investigating the effects of systemically administered strontium ranelate on alveolar bone loss histomorphometrically and histopathologically on experimental periodontitis in rats. J Periodontol. 88:e24–e31. 2017.PubMed/NCBI View Article : Google Scholar
11	Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, et al: Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 444:337–342. 2006.PubMed/NCBI View Article : Google Scholar
12	Baur JA and Sinclair DA: Therapeutic potential of resveratrol: The in vivo evidence. Nat Rev Drug Discov. 5:493–506. 2006.PubMed/NCBI View Article : Google Scholar
13	Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, Jin G, Zheng B, Kennedy BK, Suh Y, et al: Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 16:738–750. 2012.PubMed/NCBI View Article : Google Scholar
14	Shakibaei M, Shayan P, Busch F, et al: Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: potential role of Runx2 deacetylation. PLoS One. 7(e35712)2012.PubMed/NCBI View Article : Google Scholar
15	Zhang H, Zhang H, Zhang Y, Ng SS, Ren F, Wang Y, Duan Y, Chen L, Zhai Y, Guo Q and Chang Z: Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex. Cell Signal. 22:1753–1760. 2010.PubMed/NCBI View Article : Google Scholar
16	Gao X, Ge J, Li W, Zhou W and Xu L: Lncrna kcnq1ot1 promotes osteogenic differentiation to relieve osteolysis via wnt/β-catenin activation. Cell Biosci. 8(19)2018.PubMed/NCBI View Article : Google Scholar
17	Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT and Zon LI: Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 136:1136–1147. 2009.PubMed/NCBI View Article : Google Scholar
18	Komiya Y and Habas R: Wnt signal transduction pathways. Organogenesis. 4:68–75. 2008.PubMed/NCBI View Article : Google Scholar
19	Jing H, Su X, Gao B, et al: Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis. Cell Death Dis. 9(176)2018.PubMed/NCBI View Article : Google Scholar
20	Lucero CM, Vega OA, Osorio MM, Tapia JC, Antonelli M, Stein GS, van Wijnen AJ and Galindo MA: The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines. J Cell Physiol. 228:714–723. 2013.PubMed/NCBI View Article : Google Scholar
21	Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, et al: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 89:755–764. 1997.PubMed/NCBI View Article : Google Scholar
22	Simic P, Zainabadi K, Bell E, Sykes DB, Saez B, Lotinun S, Baron R, Scadden D, Schipani E and Guarente L: SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating beta-catenin. EMBO Mol Med. 5:430–440. 2013.PubMed/NCBI View Article : Google Scholar
23	Yang S, Yu H, Gong W, Wu B, Mayton L, Costello R and Wooley PH: Murine model of prosthesis failure for the long term study of aseptic loosening. J Orthop Res. 25:603–611. 2007.PubMed/NCBI View Article : Google Scholar
24	Geng D, Xu Y, Yang H, Wang J, Zhu X, Zhu G and Wang X: Protection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonist. Biomaterials. 31:1996–2000. 2010.PubMed/NCBI View Article : Google Scholar
25	Clohisy JC, Hirayama T, Frazier E, Han SK and Abu-Amer Y: NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis. J Orthop Res. 22:13–20. 2004.PubMed/NCBI View Article : Google Scholar
26	von Knoch M, Jewison DE, Sibonga JD, Sprecher C, Morrey BF, Loer F, Berry DJ and Scully SP: The effectiveness of polyethylene versus titanium particles in inducing osteolysis in vivo. J Orthop Res. 22:237–243. 2004.PubMed/NCBI View Article : Google Scholar
27	Gu Z, Chu L and Han Y: Therapeutic effect of resveratrol on mice with depression. Exp Ther Med. 17:3061–3064. 2019.PubMed/NCBI View Article : Google Scholar
28	Chen HY, Lin PH, Shih YH, Wang KL, Hong YH, Shieh TM, Huang TC and Hsia SM: Natural antioxidant resveratrol suppresses uterine fibroid cell growth and extracellular matrix formation in vitro and in vivo. Antioxidants (Basel). 8(99)2019.PubMed/NCBI View Article : Google Scholar
29	Grewal AK, Singh N and Singh TG: Effects of resveratrol postconditioning on cerebral ischemia in mice: Role of the sirtuin-1 pathway. Can J Physiol Pharmacol. 97:1094–1101. 2019.PubMed/NCBI View Article : Google Scholar
30	Bourne RB, Laskin RS and Guerin JS: Ten-year results of the first 100 genesis II total knee replacement procedures. Orthopedics. 30 (Suppl 8):S83–S85. 2007.PubMed/NCBI
31	Zhu YY, Wang ZJ, Ma N and Zhou JW: Proliferation and apoptosis of lung cancer cells regulated by gultaredoxin 3. Zhonghua Zhong Liu Za Zhi. 40:325–329. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
32	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.PubMed/NCBI View Article : Google Scholar
33	Rybchyn MS, Slater M, Conigrave AD and Mason RS: An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. J Biol Chem. 286:23771–23779. 2011.PubMed/NCBI View Article : Google Scholar
34	Xie J, Zhang X and Zhang L: Negative regulation of inflammation by SIRT1. Pharmacol Res. 67:60–67. 2013.PubMed/NCBI View Article : Google Scholar
35	Zhang C, Feng Y, Qu S, Wei X, Zhu H, Luo Q, Liu M, Chen G and Xiao X: Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53. Cardiocasc Res. 90:538–545. 2011.PubMed/NCBI View Article : Google Scholar
36	Kaeberlein M, McVey M and Guarente L: The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13:2570–2580. 1999.PubMed/NCBI View Article : Google Scholar
37	Rubiolo JA, López-Alonso H, Martín-Vázquez V, Fol-Rodríguéz N, Vieytes MR and Vega FV: Resveratrol inhibits proliferation of primary rat hepatocytes in G0/G1 by inhibiting DNA synthesis. Folia Biol (Praha). 58:166–172. 2012.PubMed/NCBI
38	Matsuda Y, Minagawa T, Okui T and Yamazaki K: Resveratrol suppresses the alveolar bone resorption induced by artificial trauma from occlusion in mice. Oral Dis. 24:412–421. 2018.PubMed/NCBI View Article : Google Scholar
39	Atienzar AN, Camacho-Alonso F and Lopez-Jornet P: Effects of resveratrol and irradiation upon oral squamous cell carcinoma cells. Acta Odontol Scand. 72:481–488. 2014.PubMed/NCBI View Article : Google Scholar
40	Kim MO, Jung H, Kim SC, Park JK and Seo YK: Electromagnetic fields and nanomagnetic particles increase the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Int J Mol Med. 35:153–160. 2015.PubMed/NCBI View Article : Google Scholar
41	Erdem A, Metzler D, Cha DK and Huang CP: The short-term toxic effects of TiO₂ nanoparticles toward bacteria through viability, cellular respiration, and lipid peroxidation. Environ Sci Pollut Res Int. 22:17917–17924. 2015.PubMed/NCBI View Article : Google Scholar
42	Deng Z, Jin J, Wang Z, Wang Y, Gao Q and Zhao J: The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening. Int J Nanomedicine. 12:3617–3636. 2017.PubMed/NCBI View Article : Google Scholar
43	Lee AM, Shandala T, Nguyen L, Muhlhausler BS, Chen KM, Howe PR and Xian CJ: Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats. Nutrients. 6:5871–5887. 2014.PubMed/NCBI View Article : Google Scholar
44	Zainabadi K, Liu CJ and Guarente L: SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2. PLoS One. 12(e0178520)2017.PubMed/NCBI View Article : Google Scholar
45	Pirapaharan DC, Olesen JB, Andersen TL, Christensen SB, Kjærsgaard-Andersen P, Delaisse JM and Søe K: Catabolic activity of osteoblast lineage cells contributes to osteoclastic bone resorption in vitro. J Cell Sci. 132(jcs229351)2019.PubMed/NCBI View Article : Google Scholar