Role of estrone on the regulation of osteoblastogenesis

Mol Cell Endocrinol. 2019 Dec 1:498:110582. doi: 10.1016/j.mce.2019.110582. Epub 2019 Sep 13.

Abstract

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.

Keywords: Cell differentiation; Estrone; Molecular mechanism; Osteoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Estrogens / pharmacology*
  • Estrone / pharmacology*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / drug effects*
  • Nitric Oxide / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Estrogens
  • Runx2 protein, rat
  • Estrone
  • Nitric Oxide
  • Alkaline Phosphatase