Related Experiment Video
Updated: Jun 23, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Development of osteoarthritic features in estrogen receptor knockout mice
Y H Sniekers1, G J V M van Osch, A G H Ederveen
1Department of Orthopaedics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Objective:
Estrogens are suggested to play a role in the development of osteoarthritis as indicated by the increased prevalence in women after menopause. We studied whether deletion of the estrogen receptor (ER) alpha, beta, or both in female mice results in cartilage damage, osteophytosis, and changes in subchondral bone of skeletally mature animals.
Methods:
We studied knee joints of 6-month-old female ERalpha-/-, ERbeta-/-, and (double) ERalpha-/-beta-/- mice and their wild type (wt) littermates. The presence and size of osteophytes and osteoarthritic changes in cartilage were analyzed using histology. Changes in subchondral plate and trabecular bone were studied using micro-CT.
Results:
In ERalpha-/-beta-/- mice, we observed an increase in number and/or size of osteophytes and thinning of the lateral subchondral plate. However, cartilage damage was not different from wt. In ERalpha-/- or ERbeta-/- mice, no significant differences in cartilage damage score, osteophyte formation, or subchondral plate thickness were found. The bone volume fraction of the epiphyseal trabecular bone was unchanged in ERalpha-/- mice, increased in ERbeta-/- mice, and decreased in ERalpha-/-beta-/- mice.
Conclusions:
We conclude that deletion of both ERs leads to increased osteophytosis, but deletion of one or both ERs does not lead to overt cartilage damage in 6-month-old mice.
Insights
Deleting both estrogen receptors (ERalpha and ERbeta) in female mice increased osteophyte formation but did not cause cartilage damage, suggesting a role for ERs in osteoarthritis development.
Area of Science:
- Endocrinology
- Rheumatology
- Skeletal Biology
Background:
- Estrogens are implicated in osteoarthritis (OA) development, evidenced by higher prevalence in postmenopausal women.
- Estrogen receptors (ERalpha and ERbeta) mediate estrogenic effects.
Purpose of the Study:
- To investigate the role of ERalpha, ERbeta, or both in OA development.
- To assess cartilage damage, osteophytosis, and subchondral bone changes in female mice lacking ERs.
Main Methods:
- Knee joints from 6-month-old female ERalpha-/-, ERbeta-/-, and ERalpha-/-beta-/- mice and wild-type littermates were analyzed.
- Histology was used to evaluate osteophytes and cartilage damage.
- Micro-CT assessed subchondral plate and trabecular bone alterations.
Main Results:
- ERalpha-/-beta-/- mice exhibited increased osteophyte formation and lateral subchondral plate thinning compared to wild-type.
- No significant differences in cartilage damage were observed between knockout and wild-type mice.
- Trabecular bone volume fraction varied: unchanged in ERalpha-/-, increased in ERbeta-/-, and decreased in ERalpha-/-beta-/- mice.
Conclusions:
- Deletion of both ERalpha and ERbeta leads to increased osteophytosis in mature female mice.
- Loss of one or both ERs did not result in overt cartilage damage at 6 months of age.
