Cited by 251Bone Metabolism and DiseasesEstrogen and related hormone effectsBone health and osteoporosis research

Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells

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Streicher, Carmen, Heyny, Alexandra, Andrukhova, Olena, Haigl, Barbara, Slavic, Svetlana, Schüler, Christiane, Kollmann, Karoline, Kantner, Ingrid +5 more·2017·Scientific Reports

Abstract

Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in part, by modulating the expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which estrogen acts on bone are still a matter of controversy. By using murine reconstitution models that allow for selective deletion of estrogen receptor-alpha (ERα) or selective inhibition of RANKL in hematopoietic vs. mesenchymal cells, in conjunction with in situ expression profiling in bone cells, we identified bone lining cells as important gatekeepers of estrogen-controlled bone resorption. Our data indicate that the increase in bone resorption observed in states of estrogen deficiency in mice is mainly caused by lack of ERα-mediated suppression of RANKL expression in bone lining cells.

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  • Osteoclast fusion requires RANKL, which is highly expressed by BLCs, osteoblasts in the growing skeleton, and osteocyte arborizations that reach the bone surface in adults.

    “Fusion also requires RANKL, which is highly expressed by BLCs;161 osteoblasts in the growing skeleton; and osteocyte arborizations that reach the bone surface in adults.51,52”

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Authors
Streicher, C., Heyny, A., Andrukhova, O., Haigl, B., Slavic, S., Schüler, C., Kollmann, K., Kantner, I., Sexl, V., Kleiter, M., Hofbauer, L. C., Kostenuik, P. J., & Erben, R. G.
Affiliations
  • University of Veterinary Medicine Vienna (AT)
  • Technische Universität Dresden (DE)
  • Amgen (United States) (US)
Corresponding author
Erben, Reinhold G.
Venue
Scientific Reports
Published
2017-07-25
Volume
7
Issue
1
Pages
6460-6460
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2738919786
Cited by
251
References
69
Citations by year
2026: 30 · 2025: 36 · 2024: 32 · 2023: 29 · 2022: 40 · 2021: 26 · 2020: 25 · 2019: 18 · 2018: 13 · 2017: 1
FWCI
6.37
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Austrian Science Fund (FWF P 21904-B11)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
estrogen, estrogen receptor alpha, RANKL, bone lining cells, bone resorption, bone turnover, bone remodeling, estrogen deficiency, osteoclasts, skeletal homeostasis, hematopoietic cells, mesenchymal cells
MeSH terms
Alkaline Phosphatase, Animals, Bone and Bones, Estrogens, Female, Gene Expression Regulation, Humans, Isoenzymes, Mice, Transgenic, Rats, Inbred F344, Bone Density, Bone Marrow Transplantation, Bone Remodeling, Mice, Knockout, Estrogen Receptor alpha, RANK Ligand, GPI-Linked Proteins, Mesenchymal Stem Cells

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