ArticleThe Journal of biological chemistry2013
Estrogen receptor α mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute down-regulation of the Wnt antagonist Sost is mediated by estrogen receptor β.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Understanding Bone Metabolism Biomarker Variability Across the Menstrual Cycle: A Systematic Review.Calcified tissue international · 2026Pooled it
- Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study.European journal of clinical nutrition · 2015Trial
- Prognostic value of serum estradiol and sclerostin for predicting fracture healing in postmenopausal women with osteoporotic vertebral compression fractures.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Sex-dependent variation in bone adaptation: from degeneration to regeneration.Journal of orthopaedic translation · 2025Review
- Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone research · 2024Review
- The hidden cross talk between bone and tissues through bone turnover.Advances in laboratory medicine · 2024Article
- Article
- Evaluation of Antioxidant Effects of Pumpkin (Antioxidants (Basel, Switzerland) · 2024Article
- Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy.Bone research · 2024Article
- Article
- Synchronisation of apical constriction and cell cycle progression is a conserved behaviour of pseudostratified neuroepithelia informed by their tissue geometry.Developmental biology · 2023Article
- Osteocyte Estrogen Receptor β (Ot-ERβ) Regulates Bone Turnover and Skeletal Adaptive Response to Mechanical Loading Differently in Male and Female Growing and Adult Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Deletion of osteopontin or bone sialoprotein induces opposite bone responses to mechanical stimulation in mice.Bone reports · 2022Article
- GATA4 and estrogen receptor alpha bind at SNPs rs9921222 and rs10794639 to regulate AXIN1 expression in osteoblasts.Human genetics · 2022Article
- Activation of canonical Wnt signaling accelerates intramembranous bone regeneration in male mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Article
- Sclerostin: From Molecule to Clinical Biomarker.International journal of molecular sciences · 2022Review
- Identification of Potentially Pathogenic Variants Associated with Recurrence in Medication-Related Osteonecrosis of the Jaw (MRONJ) Patients Using Whole-Exome Sequencing.Journal of clinical medicine · 2022Article
- Identification of Di/Tripeptide(s) With Osteoblasts Proliferation Stimulation Abilities of Yak Bone Collagen byFrontiers in nutrition · 2022Article
- Osteocyte Wnt/β-catenin pathway activation upon mechanical loading is altered in ovariectomized mice.Bone reports · 2021Article
- Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells.Cells · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Mechanical strain and estrogens both stimulate osteoblast proliferation through estrogen receptor (ER)-mediated effects, and both down-regulate the Wnt antagonist Sost/sclerostin. Here, we investigate the differential effects of ERα and -β in these processes in mouse long bone-derived osteoblastic cells and human Saos-2 cells. Recruitment to the cell cycle following strain or 17β-estradiol occurs within 30 min, as determined by Ki-67 staining, and is prevented by the ERα antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride. ERβ inhibition with 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-β]pyrimidin-3-yl] phenol (PTHPP) increases basal proliferation similarly to strain or estradiol. Both strain and estradiol down-regulate Sost expression, as does in vitro inhibition or in vivo deletion of ERα. The ERβ agonists 2,3-bis(4-hydroxyphenyl)-propionitrile and ERB041 also down-regulated Sost expression in vitro, whereas the ERα agonist 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl]tris-phenol or the ERβ antagonist PTHPP has no effect. Tamoxifen, a nongenomic ERβ agonist, down-regulates Sost expression in vitro and in bones in vivo. Inhibition of both ERs with fulvestrant or selective antagonism of ERβ, but not ERα, prevents Sost down-regulation by strain or estradiol. Sost down-regulation by strain or ERβ activation is prevented by MEK/ERK blockade. Exogenous sclerostin has no effect on estradiol-induced proliferation but prevents that following strain. Thus, in osteoblastic cells the acute proliferative effects of both estradiol and strain are ERα-mediated. Basal Sost down-regulation follows decreased activity of ERα and increased activity of ERβ. Sost down-regulation by strain or increased estrogens is mediated by ERβ, not ERα. ER-targeting therapy may facilitate structurally appropriate bone formation by enhancing the distinct ligand-independent, strain-related contributions to proliferation of both ERα and ERβ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.