Abstract
Estrogens play an important role in bone growth and maturation as well as in the regulation of bone turnover in adults. Although the effects of 17β-estradiol (E2) are well documented in long bones and vertebrae, little is known regarding its action in the mandible. E2 actions could be mediated by estrogen receptor (ER) α or β. ERs act primarily as transcriptional factors through two activation functions (AFs), AF1 and AF2, but they can also elicit membrane-initiated steroid signaling (MISS). The aim of the present study was to define ER pathways involved in E2 effects on mandibular bone. Using mice models targeting ERβ or ERα, we first show that E2 effects on mandibular bone are mediated by ERα and do not require ERβ. Second, we show that nuclear ERαAF2 is absolutely required for all the actions of E2 on mandibular bone. Third, inactivation of ERαMISS partially reduced the E2 response on bone thickness and volume, whereas there was no significant impact on bone mineral density. Altogether, these results show that both nuclear and membrane ERα are requested to mediate full estrogen effects in the mandible of growing mice. Finally, selective activation of ERαMISS is able to exert an effect on alveolar bone but not on the cortical compartment, contrary to its protective action on femoral cortical bone. To conclude, these results highlight similarities but also specificities between effects of estrogen in long bones and in the mandible that could be of interest in therapeutic approaches to treat bone mass reduction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1520-1531 |
| Number of pages | 12 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 33 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2018 |
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Keywords
- BONE QCT/µCT
- BONE REMODELING
- ESTROGENS
- GENETIC ANIMAL MODELS
- SERMS
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine
Cite this
Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice : Implications for ERα modulation. / Vinel, Alexia; Coudert, Amelie E.; Buscato, Melissa; Valera, Marie Cécile; Ostertag, Agnès; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.; Berdal, Ariane; Babajko, Sylvie; Arnal, Jean François; Fontaine, Coralie.
In: Journal of Bone and Mineral Research, Vol. 33, No. 8, 08.2018, p. 1520-1531.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice
T2 - Implications for ERα modulation
AU - Vinel, Alexia
AU - Coudert, Amelie E.
AU - Buscato, Melissa
AU - Valera, Marie Cécile
AU - Ostertag, Agnès
AU - Katzenellenbogen, John A.
AU - Katzenellenbogen, Benita S.
AU - Berdal, Ariane
AU - Babajko, Sylvie
AU - Arnal, Jean François
AU - Fontaine, Coralie
PY - 2018/8
Y1 - 2018/8
N2 - Estrogens play an important role in bone growth and maturation as well as in the regulation of bone turnover in adults. Although the effects of 17β-estradiol (E2) are well documented in long bones and vertebrae, little is known regarding its action in the mandible. E2 actions could be mediated by estrogen receptor (ER) α or β. ERs act primarily as transcriptional factors through two activation functions (AFs), AF1 and AF2, but they can also elicit membrane-initiated steroid signaling (MISS). The aim of the present study was to define ER pathways involved in E2 effects on mandibular bone. Using mice models targeting ERβ or ERα, we first show that E2 effects on mandibular bone are mediated by ERα and do not require ERβ. Second, we show that nuclear ERαAF2 is absolutely required for all the actions of E2 on mandibular bone. Third, inactivation of ERαMISS partially reduced the E2 response on bone thickness and volume, whereas there was no significant impact on bone mineral density. Altogether, these results show that both nuclear and membrane ERα are requested to mediate full estrogen effects in the mandible of growing mice. Finally, selective activation of ERαMISS is able to exert an effect on alveolar bone but not on the cortical compartment, contrary to its protective action on femoral cortical bone. To conclude, these results highlight similarities but also specificities between effects of estrogen in long bones and in the mandible that could be of interest in therapeutic approaches to treat bone mass reduction.
AB - Estrogens play an important role in bone growth and maturation as well as in the regulation of bone turnover in adults. Although the effects of 17β-estradiol (E2) are well documented in long bones and vertebrae, little is known regarding its action in the mandible. E2 actions could be mediated by estrogen receptor (ER) α or β. ERs act primarily as transcriptional factors through two activation functions (AFs), AF1 and AF2, but they can also elicit membrane-initiated steroid signaling (MISS). The aim of the present study was to define ER pathways involved in E2 effects on mandibular bone. Using mice models targeting ERβ or ERα, we first show that E2 effects on mandibular bone are mediated by ERα and do not require ERβ. Second, we show that nuclear ERαAF2 is absolutely required for all the actions of E2 on mandibular bone. Third, inactivation of ERαMISS partially reduced the E2 response on bone thickness and volume, whereas there was no significant impact on bone mineral density. Altogether, these results show that both nuclear and membrane ERα are requested to mediate full estrogen effects in the mandible of growing mice. Finally, selective activation of ERαMISS is able to exert an effect on alveolar bone but not on the cortical compartment, contrary to its protective action on femoral cortical bone. To conclude, these results highlight similarities but also specificities between effects of estrogen in long bones and in the mandible that could be of interest in therapeutic approaches to treat bone mass reduction.
KW - BONE QCT/µCT
KW - BONE REMODELING
KW - ESTROGENS
KW - GENETIC ANIMAL MODELS
KW - SERMS
UR - http://www.scopus.com/inward/record.url?scp=85047498596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047498596&partnerID=8YFLogxK
U2 - 10.1002/jbmr.3434
DO - 10.1002/jbmr.3434
M3 - Article
C2 - 29624728
AN - SCOPUS:85047498596
VL - 33
SP - 1520
EP - 1531
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 8
ER -