Adenovirus-mediated small interfering RNA targeting tumor necrosis factor-α inhibits titanium particle-induced osteoclastogenesis and bone resorption

  • Authors:
    • Haohui Guo
    • Jian Zhang
    • Shaowen Hao
    • Qunhua Jin
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  • Published online on: June 11, 2013     https://doi.org/10.3892/ijmm.2013.1416
  • Pages: 296-306
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Abstract

Wear particles are phagocytosed by macrophages, resulting in cellular activation and the release of pro-inflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty (TJA) failure. During this pathological process, tumor necrosis factor (TNF)-α plays an important role in wear particle-induced osteolysis. Therefore, in this study, we used adenovirus-mediated small interfering RNA (siRNA) targeting TNF-α to suppress the TNF-α release from activated macrophages in response to titanium particles. Our results showed that recombinant adenovirus (Ad-TNF-α-siRNA) suppressed the TNF-α release from activated macrophages in response to titanium particles, and reduced titanium particle-induced osteoclastogenesis and bone resorption in the presence of receptor activator of nuclear factor-κB ligand (RANKL). In addition, the conditioned medium of macrophages challenged with titanium particles (Ti CM) stimulated osteoprogenitor RANKL expression. The conditioned medium of macrophages challenged with titanium particles and Ad-TNF-α-siRNA (Ti-Ad CM) reduced the mRNA expression in MC3T3-E1 cells compared to Ti CM. Based on these data, TNF-α strongly synergizes with RANKL to promote osteoclast differentiation. Furthermore, TNF-α promoted osteoclast differentiation by stimulating osteoprogenitor RANKL expression. Ad-TNF‑α-siRNA effectively suppressed osteoclast differentiation and bone resorption following exposure to titanium particles in the presence of RANKL. In addition, recombinant adenovirus (Ad-TNF-α-siRNA) does not have a toxic effect on the murine macrophage cell line, RAW264.7. Consequently, it can be concluded that recombinant adenovirus-mediated siRNA targeting TNF‑α (Ad-TNF‑α-siRNA) may provide a novel therapeutic approach for the treatment of periprosthetic osteolysis.
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August 2013
Volume 32 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
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
APA
Guo, H., Zhang, J., Hao, S., & Jin, Q. (2013). Adenovirus-mediated small interfering RNA targeting tumor necrosis factor-α inhibits titanium particle-induced osteoclastogenesis and bone resorption. International Journal of Molecular Medicine, 32, 296-306. https://doi.org/10.3892/ijmm.2013.1416
MLA
Guo, H., Zhang, J., Hao, S., Jin, Q."Adenovirus-mediated small interfering RNA targeting tumor necrosis factor-α inhibits titanium particle-induced osteoclastogenesis and bone resorption". International Journal of Molecular Medicine 32.2 (2013): 296-306.
Chicago
Guo, H., Zhang, J., Hao, S., Jin, Q."Adenovirus-mediated small interfering RNA targeting tumor necrosis factor-α inhibits titanium particle-induced osteoclastogenesis and bone resorption". International Journal of Molecular Medicine 32, no. 2 (2013): 296-306. https://doi.org/10.3892/ijmm.2013.1416