Identification of estrogen-regulated genes of potential importance for the regulation of trabecular bone mineral density.
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 17beta-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 beta (TGF-beta), 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 alpha (ER-alpha)-mediated (5/7) while some genes (2/7) were regulated both via ER-alpha and ER-beta. 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.
Lindberg
Marie K
MK
Center for Bone Research at the Sahlgrenska Academy, Division of Endocrinology, Department of Internal Medicine, Göteborgs Universitet. Göteborg, Sweden.
Movérare
Sofia
S
Eriksson
Anna-Lena
AL
Skrtic
Stanko
S
Gao
Hui
H
Dahlman-Wright
Karin
K
Gustafsson
Jan-Ake
JA
Ohlsson
Claes
C
D000818:Animals; D001483:Base Sequence; D015519:Bone Density; D017931:DNA Primers; D004967:Estrogens / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL
D017931:DNA Primers; D004967:Estrogens