Role of estrone on the regulation of osteoblastogenesis

Although estradiol bone contribution has been deeply studied, little is known about the action of estrone. We investigated the direct action of estrone on osteoblasts growth and differentiation, with focus on the biochemical mechanism displayed by the estrogen. Murine calvarial osteoblast cultures in vitro exposed to 10 nM estrone were employed. Estrone enhanced gene expression of the osteogenic differentiation marker, Runx2 mRNA (150% above control). The hormone significantly increased cell proliferation (38% above control), nitric oxide production (108% above control), alkaline phosphatase activity (50% above control), in addition to stimulation of extracellular matrix mineralization. Using specific antagonists, we found that the mechanism of action of estrone involves estrogen receptor, nitric oxide synthase and MAPK signalling pathways participation. The hormone acts by its own and probably not via conversion to estradiol, since 17 B HSD inhibition did not affect the hormonal action. This work shows a novel action of estrone on bone cells promoting osteoblastogenesis.