Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
Artikel i vetenskaplig tidskrift, 2004

To determine the long-term role of ER beta in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. Our results show that ER beta inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. INTRODUCTION: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER) alpha-/- and the ER alpha-/- beta-/-, but not the ER beta-/-, mouse models have clearly increased serum levels of estradiol. MATERIALS AND METHODS: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. RESULTS: Young adult (4-month-old) ER beta-/- mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER beta inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER alpha-/- mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER alpha-/- mice, must be mediated through ER beta because old ER alpah-/- beta-/- mice displayed unchanged, unfused growth plates. CONCLUSIONS: Our results confirm that ER beta is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER beta, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice.

growth & development

Cell Division

Estrogen Receptor alpha

anatomy & histology

Mice

cytology

growth & development

Estrogen

Tibia

Receptors

cytology

Estrogen Receptor beta

anatomy & histology

Animals

Knockout

physiology

anatomy & histology

Femur

Body Weights and Measures

Apoptosis

Absorptiometry

cytology

growth & development

genetics

physiology

cytology

cytology

physiology

Mice

growth & development

anatomy & histology

Cell Size

Chondrocytes

Age Factors

Growth Plate

physiology

Female

Intervertebral Disk

Bone Development

Cell Count

Photon

metabolism

physiology

Spine

Författare

A S Chagin

Marie K Lindberg

Göteborgs universitet

Niklas Andersson

Göteborgs universitet

Sofia Movérare-Skrtic

Göteborgs universitet

J A Gustafsson

Lars Sävendahl

Claes Ohlsson

Göteborgs universitet

Journal of Bone and Mineral Research

0884-0431 (ISSN)

Vol. 19 1 72-7

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

PubMed

14753739