Identification of estrogen-regulated genes of potential importance for the regulation of trabecular bone mineral density

Marie K. Lindberg, Sofia Movérare, Anna Lena Eriksson, Stanko Skrtic, Hui Gao, Karin Dahlman-Wright, Jan Åke Gustafsson, Claes Ohlsson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Estrogen is of importance for the regulation of trabecular bone mineral density (BMD). The aim of this study was to search for possible mechanisms of action of estrogen on bone. Ovariectomized (OVX) mice were treated with 17β-estradiol. Possible effects of estrogen on the expression of 125 different bone-related genes in humerus were analyzed using the microarray technique. Estrogen regulated 12 of these genes, namely, two growth factor-related genes, 8 cytokines, and 2 bone matrix-related genes. Five of the 12 genes are known to be estrogen-regulated, and the remaining 7 genes are novel estrogen-regulated genes. Seven genes, including interleukin-1 receptor antagonist (IL-1ra), IL-1receptor type II (IL-1RII), insulin-like growth factor-binding protein 4 (IGFBP-4), transforming growth factor β (TGF-β), granulocyte colony-stimulating factor receptor (G-CSFR), leukemia inhibitory factor receptor (LIFR), and soluble IL-4 receptor (sIL-4R) were selected as probable candidate genes for the trabecular bone-sparing effect of estrogen, as the mRNA levels of these genes were highly correlated (r2 > 0.65) to the trabecular BMD. The regulation of most of these seven genes was predominantly estrogen receptor α (ER-α)-mediated (5/7) while some genes (2/7) were regulated both via ER-α and ER-β. In conclusion, by using the microarray technique, we have identified four previously known and three novel estrogen-regulated genes of potential importance for the trabecular bone-sparing effect of estrogen.

Original languageEnglish (US)
Pages (from-to)2183-2195
Number of pages13
JournalJournal of Bone and Mineral Research
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2002

Keywords

  • Estrogen
  • Insulin-like growth factor binding protein 4
  • Interleukin-1
  • Leukemia inhibitory factor receptor
  • Microarray
  • Trabecular bone mineral density
  • Transforming growth factor β

ASJC Scopus subject areas

  • Surgery

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