Cadmium induces differentiation of RAW264.7 cells into osteoclasts in the presence of RANKL.

Abstract The mechanism of cadmium effects on bone is not fully understood. In this study, we investigated the effects of cadmium on osteoclasts differentiation and the probable mechanism. RAW264.7 cells were exposed to cadmium (0–60 nmol/L) in the presence or absence of receptor-activated nuclear factor κ B ligand (RANKL) for 5 days. Then, the viability, tartrate-resistant acid phosphatase (TRAP) activity and the formation of TRAP positive multinucleated osteoclasts were observed. Receptor activator of nuclear factor κ B (RANK), tumor necrosis factor receptor associated factor 6 (TRAF6), c-src, c-fos, fos-related antigen 1 (Fra1) expression were determined by reverse transcription polymerase chain reaction. Cadmium increased TRAP activity (20–40%) and TRAP positive cell formation in the presence of RANKL, but had no obvious influence on them without RANKL. RANK, TRAF6, Fra1, c-src and c-fos (at 15–30 nmol/L) expression were enhanced (30–70%) by cadmium in the presence of RANKL, but cadmium had little influence on them in the absence of RANKL. This study demonstrated that cadmium could induce differentiation of osteoclasts precursor into osteoclasts in the presence of RANKL. Even though the changes of gene expression were small, RANKL/RANK and downstream genes may play an important role in cadmium effects on osteoclasts.