Estrogen receptor-β regulates mechanical signaling in primary osteoblasts

If you need an accessible version of this item, please submit a remediation request.
Date
2014-04-15
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
American Physiological Society (APS)
Abstract

Mechanical loading is an important regulator in skeletal growth, maintenance, and aging. Estrogen receptors have a regulatory role in mechanically induced bone adaptation. Estrogen receptor-α (ERα) is known to enhance load-induced bone formation, whereas ERβ negatively regulates this process. We hypothesized that ERβ regulates mechanical signaling in osteoblasts. We tested this hypothesis by subjecting primary calvarial cells isolated from wild-type and ERβ-knockout mice (BERKO) to oscillatory fluid flow in the absence or presence of estradiol (E2). We found that the known responses to fluid shear stress, i.e., phosphorylation of the mitogen-activated protein kinase ERK and upregulation of COX-2 expression, were inhibited in BERKO cells in the absence of E2. Flow-induced increase in prostaglandin E2 (PGE2) release was not altered in BERKO cells in the absence of E2, but was increased when E2 was present. Additionally, immunofluorescence analysis and estrogen response element luciferase assays revealed increased ERα expression and flow- and ligand-induced nuclear translocation as well as transcriptional activity in BERKO cells in both the presence and absence of E2. Taken together, these data suggest that ERβ plays both ligand-dependent and ligand-independent roles in mechanical signaling in osteoblasts. Furthermore, our data suggest that one mechanism by which ERβ regulates mechanotransduction in osteoblasts may result from its inhibitory effect on ERα expression and function. Targeting estrogen receptors (e.g., inhibiting ERβ) may represent an effective approach for prevention and treatment of age-related bone loss.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Castillo, A. B., Triplett, J. W., Pavalko, F. M., & Turner, C. H. (2014). Estrogen receptor-β regulates mechanical signaling in primary osteoblasts. American Journal of Physiology - Endocrinology and Metabolism, 306(8), E937–E944. http://doi.org/10.1152/ajpendo.00458.2013
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
American Journal of Physiology - Endocrinology and Metabolism
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
This item is under embargo {{howLong}}