Estrogen receptor-β regulates mechanical signaling in primary osteoblasts

Alesha Castillo, Jason W. Triplett, Fredrick M. Pavalko, Charles H. Turner

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number8
DOIs
StatePublished - Apr 15 2014

Fingerprint

Osteoblasts
Estrogen Receptors
Ligands
Response Elements
Mitogen-Activated Protein Kinases
Luciferases
Dinoprostone
Osteogenesis
Knockout Mice
Osteoporosis
Fluorescent Antibody Technique
Estradiol
Estrogens
Up-Regulation
Maintenance
Phosphorylation
Bone and Bones

Keywords

  • Cyclooxygenase-2
  • Estrogen receptor-β
  • Mechanobiology
  • Osteoblast

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen receptor-β regulates mechanical signaling in primary osteoblasts. / Castillo, Alesha; Triplett, Jason W.; Pavalko, Fredrick M.; Turner, Charles H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 306, No. 8, 15.04.2014.

Research output: Contribution to journalArticle

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