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.