Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA

  • Authors:
    • Shouxuan Sun
    • Haohui Guo
    • Jian Zhang
    • Bo Yu
    • Kening Sun
    • Qunhua Jin
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  • Published online on: May 27, 2013     https://doi.org/10.3892/ijmm.2013.1392
  • Pages: 403-409
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Abstract

The phagocytosis of wear particles by macrophages results in the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), which play a major role in promoting osteoclast recruitment. The inhibition of TNF-α expression decreases osteoclastogenesis. In a previous study, we demonstrated that bone morphogenetic protein-2 (BMP‑2) can activate wear debris-induced osteoclast recruitment in the presence of receptor activator of nuclear factor (NF)‑κB ligand (RANKL); however, whether these effects are associated with pro-inflammatory cytokines remains unclear. In this study, we constructed an adenoviral vector carrying TNF‑small interfering RNA (siRNA) (Ad‑TNF‑siRNA), as well as a vector carrying both the BMP‑2 gene and TNF‑α‑siRNA (Ad-BMP‑2‑TNF‑siRNA). The two adenoviral vectors significantly suppressed the expression of TNF-α; however, only treatment with Ad-TNF-siRNA significantly inhibited osteoclastogenesis. We demonstrate that the overexpression of BMP‑2, despite the suppression of TNF‑α expression by Ad-BMP‑2‑TNF‑siRNA, increases the size and number of titanium (Ti) particle‑induced multinuclear osteoclasts, the expression of osteoclast genes, as well as the resorption area. There were no differences observed between Ti particle‑induced and Ad-BMP-2‑TNF-siRNA‑induced osteoclast formation. Moreover, Ad‑BMP-2‑TNF‑siRNA directly acted upon osteoclast precursors by increasing the level of c‑Fos, regulating other signaling pathways, such as p38 phosphorylated c‑Jun N-terminal kinase (p-JNK) and phosphorylated IκB (p‑IκB). Taken together, these data demonstrate that treatment with Ad-BMP-2‑TNF‑siRNA increases wear debris‑induced osteoclast formation by activating c‑Fos and that these effects are not associated with pro-inflammatory cytokines.
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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
Sun S, Guo H, Zhang J, Yu B, Sun K and Jin Q: Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA. Int J Mol Med 32: 403-409, 2013
APA
Sun, S., Guo, H., Zhang, J., Yu, B., Sun, K., & Jin, Q. (2013). Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA. International Journal of Molecular Medicine, 32, 403-409. https://doi.org/10.3892/ijmm.2013.1392
MLA
Sun, S., Guo, H., Zhang, J., Yu, B., Sun, K., Jin, Q."Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA". International Journal of Molecular Medicine 32.2 (2013): 403-409.
Chicago
Sun, S., Guo, H., Zhang, J., Yu, B., Sun, K., Jin, Q."Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA". International Journal of Molecular Medicine 32, no. 2 (2013): 403-409. https://doi.org/10.3892/ijmm.2013.1392