Activation of the osteopontin promoter by the orphan nuclear receptor estrogen receptor related alpha

Estrogen receptor related alpha (ERR alpha) is an orphan nuclear receptor t hat is closely related to the estrogen receptor. It is expressed in a varie ty of adult and embryonic tissues (in particular, at the onset of ossificat ion), as well as in several osteoblastic cell lines. ERR alpha acts as a si te-specific, cell-specific transcriptional activator. Here, we show that ER Ra transactivates the promoter of the mouse osteopontin (OPN) gene, the pro duct of which is a marker of the late stages of osteoblastic differentiatio n. This effect is cell specific and is exerted through derivatives of the E RR alpha response element. Overexpression of ERRa in three different osteob last-like cell lines results in an elevation of the amount of OPN-correspon ding mRNA. Therefore, OPN is a target gene for ERR alpha, pointing to the r ole of the latter in osteoblast differentiation.