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.

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. PMID: 23708523 [PubMed - as supplied by publisher]
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research