Skip to main content
Log in

Osteoarthritic process modifies expression response to NiTi alloy presence

  • Biocompatibility Studies
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Nickel-titanium alloy (nitinol, NiTi) is a biomaterial with unique thermal shape memory, superelasticity and high damping properties. Therefore NiTi has been used in medical applications. In this in vitro study, the effect of NiTi alloy (with two surface modifications – helium and hydrogen) on gene expression profile of selected interleukins (IL-1β, IL-6 and IL-8) and matrix metalloproteinases (MMP-1 and MMP-2) in human physiological osteoblasts and human osteoarthritic osteoblasts was examined to respond to a question of the different behavior of bone tissue in the implantation of metallic materials in the presence of cells affected by the osteoarthritic process. The cells were cultivated in contact with NiTi and with or without LPS (bacterial lipolysaccharide). Changes in expression of target genes were calculated by 2-ΔΔCt method. An increased gene expression of IL-1β in osteoarthritic osteoblasts, with even higher expression in cells collected directly from the metal surface was observed. In case of physiological osteoblasts, the change in expression was detected after LPS treatment in cells surrounding the disc. Higher expression levels of IL-8 were observed in osteoarthritic osteoblasts after NiTi treatment in contact with alloy, and in physiological osteoblasts without relation to location in combination of NiTi and LPS. IL-6 was slightly increased in physiological osteoblastes after application of LPS. MMP-1 expression level was obviously significantly higher in osteoarthritic osteoblasts with differences regarding the metal surface and location. MMP-2 expression was decreased in both cell lines after LPS treatment. In conclusion, results of present study show that the NiTi alloy and the treatment by LPS, especially repeated doses of LPS, change the gene expression of selected ILs and MMPs in human osteoblast cell cultures. Some of the changes were depicted solely to osteoarthritic osteoblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Castleman LS, Motzkin SM, Alicandri FP, Bonawit VL. Biocompatibility of nitinol alloy as an implant material. J Biomed Mater Res. 1976;10:695–731.

    Article  CAS  Google Scholar 

  2. Khasenov BP, Kadnikov AA, Rabkin DI. Use in technology and medicine of TiNi alloys revealing the shape memory effect. Met Sci Heat Treat. 1988;30:300–3.

    Article  Google Scholar 

  3. Duerig TW. Present and Future Applications of Shape Memory and Superelastic Materials. MRS Online Proc. Libr. Arch. [Internet]. 1994 [cited2017 Jun 27];360. Available from: https://www.cambridge.org/core/journals/mrs-online-proceedings-library-archive/article/present-and-future-applications-of-shape-memory-and-superelastic-materials/8C81C41C01FE30B24E96408096D67562.

  4. Ryhänen J, Niemi E, Serlo W, Niemelä E, Sandvik P, Pernu H, et al. Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior in human cell cultures. J Biomed Mater Res. 1997;35:451–7.

    Article  Google Scholar 

  5. Fonte M, Saigal A. Effects of crystallographic texture directionality on the compressive stress–strain response of shape recovered polycrystalline nitinol. Scr Mater. 2010;63:320–23.

    Article  CAS  Google Scholar 

  6. Greiner C, Oppenheimer SM, Dunand DC. High strength, low stiffness, porous NiTi with superelastic properties. Acta Biomater. 2005;1:705–16.

    Article  Google Scholar 

  7. Prymak O, Bogdanski D, Köller M, Esenwein SA, Muhr G, Beckmann F, et al. Morphological characterization and in vitro biocompatibility of a porous nickel–titanium alloy. Biomaterials. 2005;26:5801–7.

    Article  CAS  Google Scholar 

  8. Wayman CM, Ōtsuka K. Shape memory materials [Internet]. Reprinted with corrections. Cambridge; New York: Cambridge University Press; 1998. http://trove.nla.gov.au/work/23711130.

    Google Scholar 

  9. Shabalovskaya SA. On the nature of the biocompatibility and on medical applications of NiTi shape memory and superelastic alloys. Biomed Mater Eng. 1996;6:267–89.

    CAS  Google Scholar 

  10. Leucht P, Kim J-B, Wazen R, Currey JA, Nanci A, Brunski JB, et al. Effect of mechanical stimuli on skeletal regeneration around implants. Bone. 2007;40:919–30.

    Article  Google Scholar 

  11. Es-Souni M, Fischer-Brandies H, Es-Souni M. Human gingival fibroblast response to electropolished NiTi surfaces. J Biomed Mater Res A. 2007;80:159–66.

    Article  Google Scholar 

  12. Lausmaa J, Mattsson L, Rolander U, Kasemo B. Chemical composition and morphology of titanium surface oxides. MRS Online Proc. Libr. Arch. [Internet]. 1985 [cited2017 Jun 27];55. Available from: https://www.cambridge.org/core/journals/mrs-online-proceedings-library-archive/article/div-classtitlechemical-composition-and-morphology-of-titanium-surface-oxidesdiv/49A8E8B4AE348E8BDB6351C773590B9D.

  13. Alvarez K, Nakajima H. Metallic scaffolds for bone regeneration. Materials. 2009;2:790–832.

    Article  CAS  Google Scholar 

  14. Denkhaus E, Salnikow K. Nickel essentiality, toxicity, and carcinogenicity. Crit Rev Oncol Hematol. 2002;42:35–56.

    Article  CAS  Google Scholar 

  15. Ševčíková J, Bártková D, Goldbergová M, Kuběnová M, Čermák J, Frenzel J, et al. On the Ni-Ion release rate from surfaces of binary NiTi shape memory alloys. Appl Surf Sci. 2018;427:434–43.

    Article  Google Scholar 

  16. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6:625–35.

    Article  CAS  Google Scholar 

  17. Wang H, Xu DX. A research review: poisonous bacteria lipopolysaccharide and development. Foreign Med Sci Hyg. 2008;35:170–3.

    CAS  Google Scholar 

  18. Shi H, Guo Y, Liu Y, Shi B, Guo X, Jin L, et al. The in vitro effect of lipopolysaccharide on proliferation, inflammatory factors and antioxidant enzyme activity in bovine mammary epithelial cells. Anim Nutr. 2016;2:99–104.

    Article  Google Scholar 

  19. Caccese RG, Zimmerman JL, Carlson RP. Bacterial lipopolysaccharide potentiates type II collagen-induced arthritis in mice. Mediat Inflamm. 1992;1:273–9.

    Article  CAS  Google Scholar 

  20. Lorenz W, Buhrmann C, Mobasheri A, Lueders C, Shakibaei M. Bacterial lipopolysaccharides form procollagen-endotoxin complexes that trigger cartilage inflammation and degeneration: implications for the development of rheumatoid arthritis. Arthritis Res Ther. 2013;15:R111.

    Article  Google Scholar 

  21. Huang Z, Stabler T, Pei F, Kraus VB. Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation Authors. Osteoarthr Cartil OARS Osteoarthr Res Soc. 2016;24:1769–75.

    Article  CAS  Google Scholar 

  22. Krasnokutsky S, Samuels J, Abramson SB. Osteoarthritis in 2007. Bull NYU Hosp Jt Dis. 2007;65:222–8.

    Google Scholar 

  23. Liu-Bryan R. Synovium and the innate inflammatory network in osteoarthritis progression. Curr Rheumatol Rep. 2013;15:323.

    Article  Google Scholar 

  24. Triantafilou M, Triantafilou K. Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol. 2002;23:301–4.

    Article  CAS  Google Scholar 

  25. Cho J-S, Kang J-H, Um J-Y, Han I-H, Park I-H, Lee H-M. Lipopolysaccharide induces pro-inflammatory cytokines and mmp production via TLR4 in nasal polyp-derived fibroblast and organ culture. PLoS ONE. 2014;9:e90683.

    Article  Google Scholar 

  26. Balkwill FR, Burke F. The cytokine network. Immunol Today. 1989;10:299–304.

    Article  CAS  Google Scholar 

  27. Hoekzema R, Murray PI, van Haren MA, Helle M, Kijlstra A. Analysis of interleukin-6 in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci. 1991;32:88–95.

    CAS  Google Scholar 

  28. Shida J, Trindade MC, Goodman SB, Schurman DJ, Smith RL. Induction of interleukin-6 release in human osteoblast-like cells exposed to titanium particles in vitro. Calcif Tissue Int. 2000;67:151–5.

    Article  CAS  Google Scholar 

  29. Kapanen A, Kinnunen A, Ryhänen J, Tuukkanen J. TGF-β1 secretion of ROS-17/2.8 cultures on NiTi implant material. Biomaterials. 2002;23:3341–6.

    Article  CAS  Google Scholar 

  30. Matsukawa A, Yoshimura T, Maeda T, Ohkawara S, Takagi K, Yoshinaga M. Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol Baltim Md 1950. 1995;154:5418–25.

    CAS  Google Scholar 

  31. Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med Off Publ Am Assoc Oral Biol. 1993;4:197–250.

    Article  CAS  Google Scholar 

  32. Pap T, Pap G, Hummel KM, Franz JK, Jeisy E, Sainsbury I, et al. Membrane-type-1 matrix metalloproteinase is abundantly expressed in fibroblasts and osteoclasts at the bone-implant interface of aseptically loosened joint arthroplasties in situ. J Rheumatol. 1999;26:166–9.

    CAS  Google Scholar 

  33. Murphy G, Nagase H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol. 2008;4:128–35.

    Article  CAS  Google Scholar 

  34. Karlsson C, Dehne T, Lindahl A, Brittberg M, Pruss A, Sittinger M, et al. Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthr Cartil. 2010;18:581–92.

    Article  CAS  Google Scholar 

  35. Westacott CI, Sharif M. Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum. 1996;25:254–72.

    Article  CAS  Google Scholar 

  36. Clements KM, Price JS, Chambers MG, Visco DM, Poole AR, Mason RM. Gene deletion of either interleukin-1beta, interleukin-1beta-converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy. Arthritis Rheum. 2003;48:3452–63.

    Article  CAS  Google Scholar 

  37. Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood. 1991;77:1627–52.

    CAS  Google Scholar 

  38. Goekoop RJ, Kloppenburg M, Kroon HM, Frölich M, Huizinga TWJ, Westendorp RGJ, et al. Low innate production of interleukin-1beta and interleukin-6 is associated with the absence of osteoarthritis in old age. Osteoarthr Cartil. 2010;18:942–7.

    Article  CAS  Google Scholar 

  39. Henrotin YE, De Groote DD, Labasse AH, Gaspar SE, Zheng SX, Geenen VG, et al. Effects of exogenous IL-1 beta, TNF alpha, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. Osteoarthr Cartil. 1996;4:163–73.

    Article  CAS  Google Scholar 

  40. Guerne PA, Carson DA, Lotz M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol Baltim Md 1950. 1990;144:499–505.

    CAS  Google Scholar 

  41. Lotz M, Terkeltaub R, Villiger PM. Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. J Immunol Baltim Md 1950. 1992;148:466–73.

    CAS  Google Scholar 

  42. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7:33–42.

    Article  CAS  Google Scholar 

  43. de Isla NG, Stoltz JF. In vitro inhibition of IL-1beta catabolic effects on cartilage: a mechanism involved on diacerein anti-OA properties. Biorheology. 2008;45:433–8.

    Google Scholar 

  44. Logar DB, Komadina R, Prezelj J, Ostanek B, Trost Z, Marc J. Expression of bone resorption genes in osteoarthritis and in osteoporosis. J Bone Miner Metab. 2007;25:219–25.

    Article  CAS  Google Scholar 

  45. Ray A, Kuroki K, Cook JL, Bal BS, Kenter K, Aust G, et al. Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis. Arthritis Rheum. 2003;48:134–45.

    Article  CAS  Google Scholar 

  46. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265:621–36.

    Article  CAS  Google Scholar 

  47. Evans CA, Jellis J, Hughes SP, Remick DG, Friedland JS. Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis. J Infect Dis. 1998;177:1582–7.

    Article  CAS  Google Scholar 

  48. Massicotte F, Lajeunesse D, Benderdour M, Pelletier J-P, Hilal G, Duval N, et al. Can altered production of interleukin-1beta, interleukin-6, transforming growth factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthr Cartil. 2002;10:491–500.

    Article  CAS  Google Scholar 

  49. Kwan Tat S, Pelletier J-P, Lajeunesse D, Fahmi H, Lavigne M, Martel-Pelletier J. The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol. 2008;26:295–304.

    CAS  Google Scholar 

  50. Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K. Essential involvement of interleukin-8 (IL-8) in acute inflammation. J Leukoc Biol. 1994;56:559–64.

    Article  CAS  Google Scholar 

  51. Takahashi A, de Andrés MC, Hashimoto K, Itoi E, Oreffo ROC. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthr Cartil. 2015;23:1946–54.

    Article  CAS  Google Scholar 

  52. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. 2000;59:455–61.

    Article  CAS  Google Scholar 

  53. Jackson MT, Moradi B, Smith MM, Jackson CJ, Little CB. Activation of matrix metalloproteinases 2, 9, and 13 by activated protein C in human osteoarthritic cartilage chondrocytes. Arthritis Rheumatol Hoboken Nj. 2014;66:1525–36.

    Article  CAS  Google Scholar 

  54. Tío L, Martel-Pelletier J, Pelletier J-P, Bishop PN, Roughley P, Farran A, et al. Characterization of opticin digestion by proteases involved in osteoarthritis development. Jt Bone Spine Rev Rhum. 2014;81:137–41.

    Article  Google Scholar 

  55. Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res Gmr. 2015;14:14811–22.

    Article  CAS  Google Scholar 

  56. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther. 2009;11:224.

    Article  Google Scholar 

  57. Sakao K, Takahashi KA, Arai Y, Saito M, Honjo K, Hiraoka N, et al. Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis. J Bone Miner Metab. 2009;27:412–23.

    Article  CAS  Google Scholar 

  58. Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des. 2011;17:2241–52.

    Article  CAS  Google Scholar 

  59. Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol Ther. 2014;144:1–11.

    Article  CAS  Google Scholar 

  60. Ishibashi T. Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Curr Pharm Des. 2013;19:6375–81.

    Article  CAS  Google Scholar 

  61. Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, et al. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016;6:18971.

    Article  CAS  Google Scholar 

  62. Yeung KWK, Poon RWY, Chu PK, Chung CY, Liu XY, Lu WW, et al. Surface mechanical properties, corrosion resistance, and cytocompatibility of nitrogen plasma-implanted nickel-titanium alloys: a comparative study with commonly used medical grade materials. J Biomed Mater Res A. 2007;82:403–14.

    Article  CAS  Google Scholar 

  63. Li Q, Xia Y-Y, Tang J-C, Wang R-Y, Bei C-Y, Zeng Y. In vitro and in vivo biocompatibility investigation of diamond-like carbon coated nickel-titanium shape memory alloy. Artif Cells Blood Substit Immobil Biotechnol. 2011;39:137–42.

    Article  CAS  Google Scholar 

  64. Sun T, Wang L-P, Wang M, Tong H-W, Lu WW. Characteristics and in vitro biological assessment of (Ti, O, N)/Ti composite coating formed on NiTi shape memory alloy. Thin Solid Films. 2011;519:4623–8.

    Article  CAS  Google Scholar 

  65. Markhoff J, Krogull M, Schulze C, Rotsch C, Hunger S, Bader R. Biocompatibility and Inflammatory Potential of Titanium Alloys Cultivated with Human Osteoblasts, Fibroblasts and Macrophages. Materials. 2017;10:52.

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge financial support from Czech Science Foundation under the contract no. 15-16336 S.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Monika Pávková Goldbergová.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Válková, L., Ševčíková, J., Pávková Goldbergová, M. et al. Osteoarthritic process modifies expression response to NiTi alloy presence. J Mater Sci: Mater Med 29, 146 (2018). https://doi.org/10.1007/s10856-018-6156-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-018-6156-z

Navigation