Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation

Alexia Vinel, Amelie E. Coudert, Melissa Buscato, Marie Cécile Valera, Agnès Ostertag, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Ariane Berdal, Sylvie Babajko, Jean François Arnal, Coralie Fontaine

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1520-1531
Number of pages12
JournalJournal of Bone and Mineral Research
Volume33
Issue number8
DOIs
StatePublished - Aug 2018

Fingerprint

Mandible
Estrogen Receptors
Bone and Bones
Membranes
Estrogens
Bone Remodeling
Bone Development
Nuclear Envelope
Thigh
Bone Density
Estradiol
Spine
Steroids

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

Vinel, A., Coudert, A. E., Buscato, M., Valera, M. C., Ostertag, A., Katzenellenbogen, J. A., ... Fontaine, C. (2018). Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation. Journal of Bone and Mineral Research, 33(8), 1520-1531. https://doi.org/10.1002/jbmr.3434

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 journalArticle

Vinel, A, Coudert, AE, Buscato, M, Valera, MC, Ostertag, A, Katzenellenbogen, JA, Katzenellenbogen, BS, Berdal, A, Babajko, S, Arnal, JF & Fontaine, C 2018, 'Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation', Journal of Bone and Mineral Research, vol. 33, no. 8, pp. 1520-1531. https://doi.org/10.1002/jbmr.3434
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. / Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice : Implications for ERα modulation. In: Journal of Bone and Mineral Research. 2018 ; Vol. 33, No. 8. pp. 1520-1531.
@article{cfddb13c9111440684a8500796ca0e38,
title = "Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation",
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.",
keywords = "BONE QCT/µCT, BONE REMODELING, ESTROGENS, GENETIC ANIMAL MODELS, SERMS",
author = "Alexia Vinel and Coudert, {Amelie E.} and Melissa Buscato and Valera, {Marie C{\'e}cile} and Agn{\`e}s Ostertag and Katzenellenbogen, {John A.} and Katzenellenbogen, {Benita S.} and Ariane Berdal and Sylvie Babajko and Arnal, {Jean Fran{\cc}ois} and Coralie Fontaine",
year = "2018",
month = "8",
doi = "10.1002/jbmr.3434",
language = "English (US)",
volume = "33",
pages = "1520--1531",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "8",

}

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 -