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


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 17 beta-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.
Parikka
Vilhelmiina
V
Department of Anatomy and Medicity Research Laboratory, University of Turku, FIN-20700 Turku, Finland. vilpar@utu.fi
Peng
ZhiQi
Z
Hentunen
Teuvo
T
Risteli
Juha
J
Elo
Teresa
T
Väänänen
H Kalervo
HK
Härkönen
Pirkko
P
D000818:Animals; D015519:Bone Density; D001846:Bone Development / Q000502:physiology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005269:Femur / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008903:Minerals; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012737:Sex Factors; D013977:Tibia / Q000473:pathology
C490916:Esrrg protein, mouse; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D008903:Minerals; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D004958:Estradiol; C028705:bone ash