Abstract
Ideal orthopedic coatings should trigger good osteogenic response and limited inflammatory response. The cerium valence states in ceria are associated with their anti-oxidative activity and anti-inflammatory property. In the study, we prepared two kinds of plasma sprayed CeO2 coatings with different Ce4+ concentrations to investigate the effects of Ce valence states on the response of bone mesenchymal stem cells (BMSCs) and macrophage RAW264.7. Both the coatings (CeO2-A and CeO2-B) were characterized via XRD, SEM, and X-ray photoelectron spectroscopy. The CeO2 coatings enhanced osteogenic behaviors of BMSCs in terms of cellular proliferation, alkaline phosphatase (ALP) activity and calcium deposition activity in comparison with the Ti substrate. In particular, the CeO2-B coating (higher Ce4+ concentration) elicited greater effects than the CeO2-A coating (higher Ce3+ concentration). RT-PCR and western blot results suggested that the CeO2-B coating promoted BMSCs osteogenic differentiation through the SMAD-dependent BMP signaling pathway, which activated Runx2 expression and subsequently enhanced the expression of ALP and OCN. With respect to either CeO2-A coating or Ti substrate, the CeO2-B coating exerted greater effects on the macrophages, increasing the anti-inflammatory cytokines (IL-10 and IL-1ra) expression and suppressing the expression of the pro-inflammatory cytokines (TNF-α and IL-6) and ROS production. Furthermore, it also upregulated the expression of osteoinductive molecules (TGF-β1 and BMP2) in the macrophages. The regulation of cerium valence states at plasma sprayed ceria coatings can be a valuable strategy to improve osteogenic properties and alleviate inflammatory response.
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References
Liu C, Li F, Ma LP, Cheng HM (2010) Advanced materials for energy storage. Adv Mater 22(8) E28-+. doi:10.1002/adma.200903328
Trovarelli A (1996) Catalytic properties of ceria and CeO2-containing materials. Catal Rev 38(4):439–520. doi:10.1080/01614949608006464
Montini T, Melchionna M, Monai M, Fornasiero P (2016) Fundamentals and catalytic applications of CeO2-based materials. Chem Rev 116(10):5987–6041. doi:10.1021/acs.chemrev.5b00603
Chen JP, Patil S, Seal S, McGinnis JF (2006) Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol 1(2):142–150. doi:10.1038/nnano.2006.91
Estevez AY, Pritchard S, Harper K, Aston JW, Lynch A, Lucky JJ, Ludington JS, Chatani P, Mosenthal WP, Leiter JC, Andreescu S, Erlichman JS (2011) Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radical Bio Med 51(6):1155–1163. doi:10.1016/j.freeradbiomed.2011.06.006
Hayat A, Bulbul G, Andreescu S (2014) Probing phosphatase activity using redox active nanoparticles: a novel colorimetric approach for the detection of enzyme activity. Biosens Bioelectron 56:334–339. doi:10.1016/j.bios.2014.01.003
Xiang JY, Li JM, He J, Tang XY, Dou C, Cao Z, Yu B, Zhao CR, Kang F, Yang L, Dong SW, Yang XC (2016) Cerium oxide nanoparticle modified scaffold Interface enhances vascularization of bone grafts by activating calcium channel of mesenchymal stem cells. Acs Appl Mater Inter 8(7):4489–4499. doi:10.1021/acsami.6b00158
Karakoti AS, Tsigkou O, Yue S, Lee PD, Stevens MM, Jones JR, Seal S (2010) Rare earth oxides as nanoadditives in 3-D nanocomposite scaffolds for bone regeneration. J Mater Chem 20(40):8912–8919. doi:10.1039/c0jm01072c
Li K, Xie YT, You MY, Huang LP, Zheng XB (2016) Plasma sprayed cerium oxide coating inhibits H2O2-induced oxidative stress and supports cell viability. J Mater Sci-Mater M 27(6). doi:10.1007/S10856-016-5710-9
Li K, Xie YT, You MY, Huang LP, Zheng XB (2016) Cerium oxide-incorporated calcium silicate coating protects MC3T3-E1 osteoblastic cells from H2O2-induced oxidative stress. Biol Trace Elem Res 174(1):198–207. doi:10.1007/s12011-016-0680-9
Banfi A, Muraglia A, Dozin B, Mastrogiacomo M, Cancedda R, Quarto R (2000) Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: implications for their use in cell therapy. Exp Hematol 28(6):707–715. doi:10.1016/S0301-472x(00)00160-0
Benoit DSW, Schwartz MP, Durney AR, Anseth KS (2008) Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater 7(10):816–823. doi:10.1038/nmat2269
Mandoli C, Pagliari F, Pagliari S, Forte G, Di Nardo P, Licoccia S, Traversa E (2010) Stem cell aligned growth induced by CeO2 nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Adv Funct Mater 20(10):1617–1624. doi:10.1002/adfm.200902363
Shoko E, Smith MF, McKenzie RH (2010) Charge distribution near bulk oxygen vacancies in cerium oxides. J Phys-Condens Mat 22(22). doi:10.1088/0953-8984/22/22/223201
Skorodumova NV, Simak SI, Lundqvist BI, Abrikosov IA, Johansson B (2002) Quantum origin of the oxygen storage capability of ceria. Phys Rev Lett 89(16). doi:10.1103/Physrevlett.89.166601
Korsvik C, Patil S, Seal S, Self WT (2007) Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem Commun 10:1056–1058. doi:10.1039/b615134e
Pirmohamed T, Dowding JM, Singh S, Wasserman B, Heckert E, Karakoti AS, King JES, Seal S, Self WT (2010) Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun 46(16):2736–2738. doi:10.1039/b922024k
Naganuma T, Traversa E (2014) The effect of cerium valence states at cerium oxide nanoparticle surfaces on cell proliferation. Biomaterials 35(15):4441–4453. doi:10.1016/j.biomaterials.2014.01.074
Williams DF (2008) On the mechanisms of biocompatibility. Biomaterials 29(20):2941–2953. doi:10.1016/j.biomaterials.2008.04.023
Chen ZT, Klein T, Murray RZ, Crawford R, Chang J, Wu CT, Xiao Y (2016) Osteoimmunomodulation for the development of advanced bone biomaterials. Mater Today 19(6):304–321. doi:10.1016/j.mattod.2015.11.004
Wu CT, Chen ZT, Wu QJ, Yi DL, Friis T, Zheng XB, Chang J, Jiang XQ, Xiao Y (2015) Clinoenstatite coatings have high bonding strength, bioactive ion release, and osteoimmunomodulatory effects that enhance in vivo osseointegration. Biomaterials 71:35–47. doi:10.1016/j.biomaterials.2015.08.027
Wu CT, Chen ZT, Yi DH, Chang J, Xiao Y (2014) Multidirectional effects of Sr-, Mg-, and Si-containing bioceramic coatings with high bonding strength on inflammation, osteoclastogenesis, and osteogenesis. Acs Appl Mater Inter 6(6):4264–4276. doi:10.1021/am4060035
Li K, Yu J, Xie Y, You M, Huang L, Zheng X (2016) The effects of cerium oxide incorporation in calcium silicate coating on bone mesenchymal stem cell and macrophage responses. Biol Trace Elem Res. doi:10.1007/s12011-016-0859-0
Selvaraj V, Manne NDPK, Arvapalli R, Rice KM, Nandyala G, Fankenhanel E, Blough ER (2015) Effect of cerium oxide nanoparticles on sepsis induced mortality and NF-B signaling in cultured macrophages. Nanomedicine-Uk 10(8):1275–1288. doi:10.2217/nnm.14.205
Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC (2008) Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappa B-dependent iNOS and proinflammatory cytokines production. Brit J Pharmacol 154(1):165–173. doi:10.1038/bjp.2008.79
Hirst SM, Karakoti AS, Tyler RD, Sriranganathan N, Seal S, Reilly CM (2009) Anti-inflammatory properties of cerium oxide nanoparticles. Small 5(24):2848–2856. doi:10.1002/smll.200901048
Huang YL, Lee CH, Liao JF, Liu YW, Chiou WF (2015) Protective effects of ugonin K on hydrogen peroxide-induced osteoblast cell damage. J Funct Foods 15:487–496. doi:10.1016/j.jff.2015.03.056
Zhang XL, Klabunde KJ (1992) Superoxide (O2-) on the surface of heat-treated ceria—intermediates in the reversible oxygen to oxide transformation. Inorg Chem 31(9):1706–1709. doi:10.1021/Ic00035a034
Pulido-Reyes G, Rodea-Palomares I, Das S, Sakthivel TS, Leganes F, Rosal R, Seal S, Fernandez-Pinas F (2015) Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states. Sci Rep-Uk 5. doi:10.1038/Srep15613
Viswanathan V, Filmalter R, Patil S, Deshpande S, Seal S (2007) High-temperature oxidation behavior of solution precursor plasma sprayed nanoceria coating on martensitic steels. J Am Ceram Soc 90(3):870–877. doi:10.1111/j.1551-2916.2006.01463.x
Pan HH, Xie YT, Li K, Hu DD, Zhao J, Zheng XB, Tang TT (2015) ROCK-regulated synergistic effect of macropore/nanowire topography on cytoskeletal distribution and cell differentiation. RSC Adv 5(123):101834–101842. doi:10.1039/c5ra19691d
Song B, Estrada KD, Lyons KM (2009) Smad signaling in skeletal development and regeneration. Cytokine Growth F R 20(5–6):379–388. doi:10.1016/j.cytogfr.2009.10.010
Jang H, Kim EJ, Park JK, Kim DE, Kim HJ, Sun WS, Hwang S, Oh KB, Koh JT, Jang WG, Lee JW (2014) SMILE inhibits BMP-2-induced expression of osteocalcin by suppressing the activity of the RUNX2 transcription factor in MC3T3E1 cells. Bone 61:10–18. doi:10.1016/j.bone.2013.12.028
Lurier E, Levy R, Barbee K, Golomb G, Spiller KL (2015) Effects of radical oxygen species and antioxidants on macrophage polarization. Northeast Bioengin C
Franz S, Rammelt S, Scharnweber D, Simon JC (2011) Immune responses to implants—a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32(28):6692–6709. doi:10.1016/j.biomaterials.2011.05.078
Hu DD, Li K, Xie YT, Pan HH, Zhao J, Huang LP, Zheng XB (2016) Different response of osteoblastic cells to Mg2+, Zn2+ and Sr2+ doped calcium silicate coatings. J Mater Sci-Mater M 27(3). doi:10.1007/s10856-016-5672-y
Hu Y, Du Y, Jiang H, Jiang GS (2014) Cerium promotes bone marrow stromal cells migration and osteogenic differentiation via Smad1/5/8 signaling pathway. Int J Clin Exp Patho 7(8):5369–5378
Liu DD, Zhang JC, Zhang Q, Wang SX, Yang MS (2013) TGF-beta/BMP signaling pathway is involved in cerium-promoted osteogenic differentiation of mesenchymal stem cells. J Cell Biochem 114(5):1105–1114. doi:10.1002/jcb.24451
Chen ZT, Wu CT, Gu WY, Klein T, Crawford R, Xiao Y (2014) Osteogenic differentiation of bone marrow MSCs by beta-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway. Biomaterials 35(5):1507–1518. doi:10.1016/j.biomaterials.2013.11.014
Ducy P, Schinke T, Karsenty G (2000) The osteoblast: a sophisticated fibroblast under central surveillance. Science 289(5484):1501–1504. doi:10.1126/science.289.5484.1501
Chen ZT, Yuen J, Crawford R, Chang J, Wu CT, Xiao Y (2015) The effect of osteoimmunomodulation on the osteogenic effects of cobalt incorporated beta-tricalcium phosphate. Biomaterials 61:126–138. doi:10.1016/j.biomaterials.2015.04.044
Mensah KA, Li J, Schwarz EM (2009) The emerging field of osteoimmunology. Immunol Res 45(2–3):100–113. doi:10.1007/s12026-009-8093-x
Veiseh O, Doloff JC, Ma ML, Vegas AJ, Tam HH, Bader AR, Li J, Langan E, Wyckoff J, Loo WS, Jhunjhunwala S, Chiu A, Siebert S, Tang K, Hollister-Lock J, Aresta-Dasilva S, Bochenek M, Mendoza-Elias J, Wang Y, Qi M, Lavin DM, Chen M, Dholakia N, Thakrar R, Lacik I, Weir GC, Oberholzer J, Greiner DL, Langer R, Anderson DG (2015) Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater 14(6):643–U125. doi:10.1038/NMAT4290
Celardo I, Pedersen JZ, Traversa E, Ghibelli L (2011) Pharmacological potential of cerium oxide nanoparticles. Nanoscale 3(4):1411–1420. doi:10.1039/c0nr00875c
Asati A, Santra S, Kaittanis C, Perez JM (2010) Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano 4(9):5321–5331. doi:10.1021/nn100816s
Acknowledgments
This work was supported by the Natural Science Foundation of China (Grant No. 51502328) and the Opening Project of the Shanghai Key Laboratory of Orthopedic Implant (Grant No. KFKT2016003).
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You, M., Li, K., Xie, Y. et al. The Effects of Cerium Valence States at Cerium Oxide Coatings on the Responses of Bone Mesenchymal Stem Cells and Macrophages. Biol Trace Elem Res 179, 259–270 (2017). https://doi.org/10.1007/s12011-017-0968-4
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DOI: https://doi.org/10.1007/s12011-017-0968-4