Overexpression of miR‑146a blocks the effect of LPS on RANKL‑induced osteoclast differentiation.

The concept that inflammation serves a leading role in osteoclast‑induced bone loss under pathological circumstances is now widely accepted. In the present study, it was observed that lipopolysaccharides (LPSs) demonstrated a synergic effect on receptor activator of nuclear factor κ‑B ligand (RANKL)‑induced osteoclast differentiation in Raw264.7 cells, with increasing levels of multiple pro‑inflammatory cytokines including interleukin (IL)‑6, tumor necrosis factor‑α and IL‑1β. Furthermore, microRNA (miR)‑146a was highly induced by LPS and RANKL co‑stimulation during the process of osteoclast differentiation. Overexpression of miR‑146a inhibited osteoclast transformation by targeting the key regulators of nuclear factor (NF)‑κβ signaling, TNF receptor‑associated factor 6 and interleukin‑1 receptor‑associated kinase 1. The downstream activation of NF‑κβ signaling was also inhibited by transfection with a miR‑146a mimic. Altogether, the results of the present study demonstrated that miR‑146a prevents osteoclast differentiation induced by LPS and RANKL co‑stimulation, suggesting that miR‑146a may be a promising therapeutic target for treatment of inflammation mediated bone loss.