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

Abstract

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.