Effects of bismuth oxide, a component of mineral trioxide aggregate, on osteoclast differentiation

Abstract

PURPOSE: Mineral trioxide aggregate (MTA) is composed of portland cement and bismuth oxide. The purpose of this study was to elucidate the effects of bismuth oxide on osteoclast differentiation.

METHODS: Bone marrow-derived macrophages (BMMs) were acquired from bone marrow of 5-week old mice. Cells were cultured with M-CSF and RANKL in the presence or absence of bismuth oxide. Multinucleated cells were counted after TRAP staining. Real-time PCR and Western blotting techniques were used to evaluate the expression levels of differentiation markers at mRNA and protein levels, respectively. Various signaling molecules were analyzed by Western blotting.

RESULTS: Bismuth oxide did not show cell cytotoxicity on bone marrow-derived macrophages at 1 uM-100 uM concentrations. Bismuth oxide increased the formation of TRAP-positive multinucleated cells. Bismuth oxide increased the expression levels of c-Fos, NFATc1 and DC-STAMP at mRNA levels and c-Fos and NFATc1 at protein levels. Bismuth oxide also activated MAPKs (p38, pJNK and pERK) among various signaling molecules involved in RANKL-induced osteoclast differentiation.

CONCLUSION: Bismuth oxide increases osteoclast differentiation by the upregulation of MAPK signaling pathways.