Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts

Bisphenol A (BPA), a major component of epoxy resins used in protective coatings, is a known endocrine-disrupting chemical. BPA has the ability of binding to estrogen receptors. In the current paper, we examine the direct effects of bisphenol A on in vitro osteoclast and osteoblast culture systems.

We evaluated the effects of BPA on osteoclast formation using bone marrow-derived macrophages and RAW 264.7 cells and on osteoblast differentiation using MC3T3-E1 cells.

BPA significantly inhibited RANKL-induced, TRAP-positive multinucleated cell formation in bone marrow-derived macrophages and RAW 264.7 cell cultures in a dose-dependent manner (0.5 μM to 12.5 μM). We observed suppression of ERK, JNK, AKT, and p38 mitogen-activated protein kinases induced by RANKL in Western blotting after BPA treatment in RAW 264.7 cells. Furthermore, BPA suppressed Bcl-2 (anti-apoptotic) while stimulating Bax (pro-apoptotic) protein expression in RAW 264.7 cells. Bisphenol A also significantly suppressed ALP activities and bone nodule formation in MC3T3-E1 cell cultures. Specifically, the expression of Bcl-2 protein was decreased, and changes in expression of caspases 3, 8, and 9 were detected by BPA treatment in both cells.

We found that bisphenol A directly suppressed both osteoclastic and osteoblastic activities in vitro. Our data suggest that bisphenol A suppresses cell differentiation and survival.