Differential expression of estrogen receptor-related receptor α and estrogen receptors α and β in osteoblasts in vivo and in vitro

Abstract

The orphan nuclear estrogen receptor-related receptor (ERR) α is expressed by osteoblastic cells, is known to transactivate at least one osteoblast-associated gene osteopontin (OPN) and plays a functional role in osteoprogenitor cell proliferation and differentiation. To dissect further the role of ERR-α in bone formation, we compared its expression to that of the estrogen receptor (ER) α and ER-β in rat calvaria (RC) and fetal tibia in vivo and in RC and rat bone marrow (RBM) cells in vitro. We found that ERR-α is highly and widely expressed in most, if not all, cells in RC cell cultures from early proliferation stages through mineralized nodule formation; ER-α was localized similarly but at lower levels and ER-β, although present, was barely detectable. These patterns of expression in vitro correlated with what we observed in vivo in sections of 21-day fetal RC, in which ERR-α appeared to be more highly expressed than either of the ERs. Interestingly, ERR-α also is highly expressed in RBM cells, while ER-α and ER-β mRNA is expressed, but at lower levels. Moreover, we found that ERR-α, ER-α, and ER-β were all expressed in osteoblasts in fetal and adult tibia whereas they were expressed differentially in calvaria in vivo in subsets of osteoblasts, supporting the hypothesis that ERR-α may interact with one or both of the ERs in those osteoblasts in which they are coexpressed and that all three receptors may be required for bone formation but at different times and for different functions.