Bisphenol A, one of the industrial chemicals used in plastics and in the coating 
of dishes and medical equipment, behaves as an endocrine disruptor in the human 
body. Bisphenol A can bind directly to several types of nuclear receptors, 
including steroid and xenobiotic receptor (SXR). SXR plays an important role in 
bone metabolism through the activation of osteoblasts in vitro, but SXR protein 
localization has not been reported in bone tissues. Additionally, it is not 
known whether bisphenol A acts on osteoblasts through SXR activation. Therefore, 
in this study, we first examined the immunolocalization of the SXR protein in 
human adult and fetal bone tissues. We then examined the effects of bisphenol A 
on human osteoblasts in vitro. SXR immunoreactivity was detected in osteoblasts, 
but not in osteoclasts, of both adult and fetal bone tissues. In fetal bone 
tissues, the mesenchymal cells or fetal connective tissue were also positive for 
SXR immunoreactivity. Expression of SXR target genes (tsukushi, matrilin-2, and 
CYP3A4) and SXR response element-luciferase activity were increased by bisphenol 
A treatment in normal osteoblasts transfected with SXR (hFOB/SXR) and in 
osteoblast-like cells (MG-63). Bisphenol A also stimulated cell proliferation 
and collagen accumulation in hFOB/SXR cells. These results suggest that, as in 
other tissues, SXR plays important roles in bone metabolism and fetal bone 
development and that bisphenol A may disturb bone homeostasis in both adult and 
fetus through SXR.