MicroRNA, a class of noncoding RNA, play a role in human diseases. MicroRNA‐146a (miR‐146a) is a negative regulator of immune and inflammatory responses, and is strongly expressed in rheumatoid arthritis (RA) synovium and peripheral blood mononuclear cells (PBMCs). This study was undertaken to examine whether miR‐146a expression inhibits osteoclastogenesis, and whether administration of miR‐146a prevents joint destruction in mice with collagen‐induced arthritis (CIA).

PBMCs from healthy volunteers were isolated and seeded in culture plates. The following day, double‐stranded miR‐146a was transfected and cultured in the presence of macrophage colony‐stimulating factor and either tumor necrosis factor α or RANKL. After 3 weeks, tartrate‐resistant acid phosphatase (TRAP)–positive multinucleated cells were counted. Three days after miR‐146a culture, the expression of c‐Jun, nuclear factor of activated T cells c1 (NF‐ATc1), PU.1, and TRAP was evaluated by quantitative reverse transcriptase–polymerase chain reaction. After the onset of distinct arthritis in mice with CIA, double‐stranded miR‐146a or nonspecific double‐stranded RNA was administered twice by intravenous injection. Radiographic and histologic examinations were performed at 4 weeks.

The number of TRAP‐positive multinucleated cells in human PBMCs was significantly reduced by miR‐146a in a dose‐dependent manner. The expression of c‐Jun, NF‐ATc1, PU.1, and TRAP in PBMCs was significantly down‐regulated by miR‐146a. Administration of miR‐146a prevented joint destruction in mice with CIA, although it did not completely ameliorate inflammation.

Our findings indicate that expression of miR‐146a inhibits osteoclastogenesis and that administration of double‐stranded miR‐146a prevents joint destruction in arthritic mice. Administration of miR‐146a has potential as a novel therapeutic target for bone destruction in RA.