Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
Journal article, 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
Author
A S Chagin
Marie K Lindberg
University of Gothenburg
Niklas Andersson
University of Gothenburg
Sofia Movérare-Skrtic
University of Gothenburg
J A Gustafsson
Lars Sävendahl
Claes Ohlsson
University of Gothenburg
Journal of Bone and Mineral Research
0884-0431 (ISSN) 15234681 (eISSN)
Vol. 19 1 72-7Subject Categories
MEDICAL AND HEALTH SCIENCES
PubMed
14753739