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The role of estrogen receptor α in the regulation of bone and growth plate cartilage.

Journal article
Authors Anna E Börjesson
Marie Lagerquist
Sara H Windahl
Claes Ohlsson
Published in Cellular and molecular life sciences : CMLS
ISSN 1420-9071
Publication year 2013
Published at Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Language en
Links dx.doi.org/10.1007/s00018-013-1317-...
Subject categories Endocrinology

Abstract

Estrogens are important endocrine regulators of skeletal growth and maintenance in both females and males. Studies have demonstrated that the estrogen receptor (ER)-α is the main mediator of these estrogenic effects in bone. Therefore, estrogen signaling via ERα is a target both for affecting longitudinal bone growth and bone remodeling. However, treatment with estradiol (E2) leads to an increased risk of side effects such as venous thromboembolism and breast cancer. Thus, an improved understanding of the signaling pathways of ERα will be essential in order to find better bone specific treatments with minimal adverse effects for different estrogen-related bone disorders. This review summarizes the recent data regarding the intracellular signaling mechanisms, in vivo, mediated by the ERα activation functions (AFs), AF-1 and AF-2, and the effect on bone, growth plate and other estrogen responsive tissues. In addition, we review the recent cell-specific ERα-deleted mouse models lacking ERα specifically in neuronal cells or growth plate cartilage. The newly characterized signaling pathways of estrogen, described in this review, provide a better understanding of the ERα signaling pathways, which may facilitate the design of new, bone-specific treatment strategies with minimal adverse effects.

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