, Volume 40, Issue 1, pp 166–173 | Cite as

Abrasive Endoprosthetic Wear Particles Inhibit IFN-γ Secretion in Human Monocytes Via Upregulating TNF-α-Induced miR-29b

  • Yan-min Bu
  • De-zhi Zheng
  • Lei Wang
  • Jun LiuEmail author


The adverse biological responses to prostheses wear particles commonly led to the failure of total hip arthroplasty. Among the released cytokines, interferon-γ (IFN-γ) has been found to be a critical functional factor during osteoclast differentiation. However, the molecular mechanism underlying the regulation of IFN-γ in wear particles-induced cells still needs to be determined. Four kinds of abrasive endoprosthetic wear particle were used to treat THP-1 cells, including polymethylmethacrylate (PMMA), zirconiumoxide (ZrO2), commercially pure titanium (cpTi), and titanium alloy (Ti-6Al-7Nb), with a concentration of 0.01, 0.05, 0.1, or 0.2 mg/ml for 48 h. The expression of IFN-γ and miR-29b was detected by real-time RT-PCR or ELISA. Luciferase reporter assay was performed to determine the regulation of miR-29b on IFN-γ. The effect of miR-29b inhibitor on the expression of wear particle-induced IFN-γ was detected. The expression of miR-29b was examined in THP-1 cells treated with tumor necrosis factor-alpha (TNF-α). The expression of IFN-γ was downregulated and the level of miR-29b was increased in THP-1 cells pretreated with wear particles. IFN-γ was a target of miR-29b. Wear particles inhibited the expression of IFN-γ through miR-29b. The expression of miR-29b was significantly reduced in THP-1 cells treated with TNF-α neutralizing antibody and particles comparing to that in the cells treated with particles alone. Wear particles inhibit the IFN-γ secretion in human monocytes, which was associated with the upregulating TNF-α-induced miR-29b.


abrasive endoprosthetic wear particles IFN-γ human monocytes TNF-α miR-29b 


Compliance with Ethical Standards

Conflict of Interest

The authors declare no actual or potential conflicts of interest.


  1. 1.
    Ulrich, S.D., et al. 2008. Total hip arthroplasties: what are the reasons for revision? International Orthopaedics 32(5): 597–604.Google Scholar
  2. 2.
    Howie, D.W., et al. 2013. Periprosthetic osteolysis after total hip replacement: molecular pathology and clinical management. Inflammopharmacology 21(6): 389–396.Google Scholar
  3. 3.
    Goodman, S., et al. 2014. Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. Journal of the Royal Society, Interface 11(93): 20130962.Google Scholar
  4. 4.
    Schroder, K., et al. 2004. Interferon-γ: an overview of signals, mechanisms and functions. Journal of Leukocyte Biology 75(2): 163–189.Google Scholar
  5. 5.
    Kohara, H., et al. 2011. IFN-γ directly inhibits TNF-α-induced osteoclastogenesis in vitro and in vivo and induces apoptosis mediated by Fas/Fas ligand interactions. Immunology Letters 137(1): 53–61.Google Scholar
  6. 6.
    Ji, J.-D., et al. 2009. Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-γ in human osteoclast precursors. The Journal of Immunology 183(11): 7223–7233.Google Scholar
  7. 7.
    Honma, M., et al. 2014. Regulatory mechanisms of RANKL presentation to osteoclast precursors. Current Osteoporosis Reports 12(1): 115–120.Google Scholar
  8. 8.
    Li, P., et al. 2016. Interferon-γ enhances the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects. Journal of Prosthodontic Research.Google Scholar
  9. 9.
    Lian, J.B., et al. 2012. MicroRNA control of bone formation and homeostasis. Nature Reviews Endocrinology 8(4): 212–227.Google Scholar
  10. 10.
    Schoolmeesters, A., et al. 2009. Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PloS One 4(5): e5605.Google Scholar
  11. 11.
    Zhou, Y., Y. Liu, and L. Cheng. 2012. miR‐21 expression is related to particle‐induced osteolysis pathogenesis. Journal of Orthopaedic Research 30(11): 1837–1842.Google Scholar
  12. 12.
    Suh, J.S., et al. 2013. Peptide-mediated intracellular delivery of miRNA-29b for osteogenic stem cell differentiation. Biomaterials 34(17): 4347–4359.Google Scholar
  13. 13.
    Kagiya, T., and S. Nakamura. 2013. Expression profiling of microRNAs in RAW264. 7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. Journal of Periodontal Research 48(3): 373–385.Google Scholar
  14. 14.
    Noordin, S., and B. Masri. 2012. Periprosthetic osteolysis: genetics, mechanisms and potential therapeutic interventions. Canadian Journal of Surgery 55(6): 408.Google Scholar
  15. 15.
    Cheng, J., et al. 2012. Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis. Journal of Interferon & Cytokine Research 32(1): 34–45.Google Scholar
  16. 16.
    Haynes, D.R., et al. 1998. Variation in cytokines induced by particles from different prosthetic materials. Clinical Orthopaedics & Related Research 352(352): 223–30.Google Scholar
  17. 17.
    Lochner, K., et al. 2011. The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles. International Journal of Molecular Medicine 28(6): 1055–63.Google Scholar
  18. 18.
    Lin, T.H., et al. 2015. Exposure of polyethylene particles induces interferon‐γ expression in a natural killer T lymphocyte and dendritic cell coculture system in vitro: A preliminary study. Journal of Biomedical Materials Research. Part A 103(1): 71–75.Google Scholar
  19. 19.
    Takayanagi, H., et al. 2005. Interplay between interferon and other cytokine systems in bone metabolism. Immunological Reviews 208(1): 181–193.Google Scholar
  20. 20.
    Duque, G., et al. 2011. Interferon‐γ plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice. Journal of Bone and Mineral Research 26(7): 1472–1483.Google Scholar
  21. 21.
    Rossi, M., et al. 2013. miR‐29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma‐related bone disease. Journal of Cellular Physiology 228(7): 1506–1515.Google Scholar
  22. 22.
    Abuna, R.P., et al. 2016. Participation of TNF‐α in Inhibitory Effects of Adipocytes on Osteoblast Differentiation. Journal of Cellular Physiology 231(1): 204–214.Google Scholar
  23. 23.
    Azuma, Y., et al. 2000. Tumor necrosis factor-α induces differentiation of and bone resorption by osteoclasts. Journal of Biological Chemistry 275(7): 4858–4864.Google Scholar
  24. 24.
    Kitaura, H., et al. 2013. Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. Clinical and Developmental Immunology. 2013.Google Scholar
  25. 25.
    Liu, N., et al. 2016. Autophagy mediated TiAl 6 V 4 particle-induced peri-implant osteolysis by promoting expression of TNF-α. Biochemical and Biophysical Research Communications 473(1): 133–139.Google Scholar
  26. 26.
    Schwarz, E.M., R.J. Looney, and R.J. O'Keefe. 2000. Anti-TNF-α therapy as a clinical intervention for periprosthetic osteolysis. Arthritis Research & Therapy 2(3): 1.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of OrthopedicsTianjin HospitalTianjinPeople’s Republic of China

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