Eur J Endocrinol
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DOI: 10.1530/eje.1.01832
European Journal of Endocrinology, Vol 152, Issue 2, 301-314
Copyright © 2005 by European Society of Endocrinology
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EXPERIMENTAL STUDY

Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-{alpha}-deficient male and female mice

Vilhelmiina Parikka1,2, ZhiQi Peng1, Teuvo Hentunen1, Juha Risteli3,4, Teresa Elo1, H Kalervo Väänänen1 and Pirkko Härkönen1,5

1 Department of Anatomy and Medicity Research Laboratory, University of Turku, FIN-20700 Turku, Finland, 2 Turku Graduate School of Biomedical Sciences, Turku, Finland, 3 Department of Clinical Chemistry, University of Oulu, FIN-90014 Oulu, Finland, 4 Department of Clinical Chemistry, University of Kuopio, FIN-70211 Kuopio, Finland, 5 Department of Laboratory Medicine, Tumor Biology, University Hospital MAS, Lund University, S-21771 Malmö, Sweden

(Correspondence should be addressed to V Parikka, Clinical Research Center, PL5000, FIN-90014 University of Oulu, Finland; Email: vilpar{at}utu.fi)

Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood.

Methods: To study the effects of long-term ER{alpha} deficiency, bone phenotype was studied in aged ER{alpha} knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro.

Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17ß-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures.

Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ER{alpha}.




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