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

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.

Inhibitory effect of quercetin on titanium particle induced endoplasmic reticulum stress related apoptosis and in vivo osteolysis

“…The results of the present study also demonstrated that QUE treatment significantly reduced Ti particle induced osteoclast differentiation in a mouse calvaria model. Increasing osteoclastogenesis and the inhibition of bone formation is the primary cause of aseptic loosening and osteolysis [ 34 ]. Growing evidence suggests that Ti particle impairs the function of mature osteoblasts as well as inducing osteoclast differentiation [ 35 – 37 ], which is consistent with the current study.…”

10−7 m 17β‐oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF‐κB pathway

“…Oestrogen deficiency usually leads to excessive expression of TNF‐α which definitively causes activation of NF‐κB . TNF‐α, a potent pro‐inflammatory cytokine, inhibits osteoblastogenesis and stimulates osteoclastogenesis under diverse inflammatory conditions . Here, it is possible that 17β‐oestradiol may induce odonto/osteoblastic differentiation of human DPSCs via activation of OR‐α/NF‐κB, but not by the canonical TNF‐α/NF‐κB pathway, and accordingly trigger differentiation‐related gene expression and mineralization .…”

Strontium ranelate inhibits wear particle-induced aseptic loosening in mice

“…Prior to injection, the granules were rinsed in 70% ethanol at room temperature for 48 h and autoclaved at 180°C for 6 h to remove endotoxins. The wear particles were tested for endotoxin using a commercial test kit (E-Toxate; Sigma, USA) ( 23 ).…”