Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion

Aaron James, Alexander A. Theologis, Samantha A. Brugmann, Yue Xu, Antoine L. Carre, Philipp Leucht, Katherine Hamilton, Kenneth S. Korach, Michael T. Longaker

Research output: Contribution to journalArticle

Abstract

Background: While premature suture fusion, or craniosynostosis, is a relatively common condition, the cause is often unknown. Estrogens are associated with growth plate fusion of endochondral bones. In the following study, we explore the previously unknown significance of estrogen/estrogen receptor signaling in cranial suture biology. Methodology/Principal Findings: Firstly, estrogen receptor (ER) expression was examined in physiologically fusing (posterofrontal) and patent (sagittal) mouse cranial sutures by quantitative RT-PCR. Next, the cranial suture phenotype of ER alpha and ER beta knockout (αERKO, βERKO) mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs) were isolated; the effects of 17-β estradiol or the estrogen antagonist Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were examined in vitro. Finally, in vivo experiments were performed in which Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed that increased ERα but not ERβ transcript abundance temporally coincided with posterofrontal suture fusion. The αERKO but not βERKO mouse exhibited delayed posterofrontal suture fusion. In vitro, addition of 17-β estradiol enhanced both osteogenic and chondrogenic differentiation in suture-derived mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo application of Fulvestrant significantly diminished calvarial osteogenesis, inhibiting suture fusion. Conclusions/Significance: Estrogen signaling through ERα but not ERβ is associated with and necessary for normal mouse posterofrontal suture fusion. In vitro studies suggest that estrogens may play a role in osteoblast and/or chondrocyte differentiation within the cranial suture complex.

Original languageEnglish (US)
Article numbere7120
JournalPLoS One
Volume4
Issue number9
DOIs
StatePublished - Sep 22 2009
Externally publishedYes

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Cranial Sutures
Estrogen Receptor alpha
sutures
Estrogen Receptors
Sutures
Estrogens
Fusion reactions
mice
estrogens
Estradiol
Estrogen Antagonists
Estrogen Receptor beta
Osteoblasts
Craniosynostoses
Growth Plate
Gene expression
estradiol
Chondrocytes
estrogen receptors
Osteogenesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

James, A., Theologis, A. A., Brugmann, S. A., Xu, Y., Carre, A. L., Leucht, P., ... Longaker, M. T. (2009). Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion. PLoS One, 4(9), [e7120]. https://doi.org/10.1371/journal.pone.0007120

Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion. / James, Aaron; Theologis, Alexander A.; Brugmann, Samantha A.; Xu, Yue; Carre, Antoine L.; Leucht, Philipp; Hamilton, Katherine; Korach, Kenneth S.; Longaker, Michael T.

In: PLoS One, Vol. 4, No. 9, e7120, 22.09.2009.

Research output: Contribution to journalArticle

James, A, Theologis, AA, Brugmann, SA, Xu, Y, Carre, AL, Leucht, P, Hamilton, K, Korach, KS & Longaker, MT 2009, 'Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion', PLoS One, vol. 4, no. 9, e7120. https://doi.org/10.1371/journal.pone.0007120
James, Aaron ; Theologis, Alexander A. ; Brugmann, Samantha A. ; Xu, Yue ; Carre, Antoine L. ; Leucht, Philipp ; Hamilton, Katherine ; Korach, Kenneth S. ; Longaker, Michael T. / Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion. In: PLoS One. 2009 ; Vol. 4, No. 9.
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