Estrogen Regulates Bone Turnover by Targeting RANKL Expression in Bone Lining Cells
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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”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [161]
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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.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-07-25
- Volume
- 7
- Issue
- 1
- Pages
- 6460-6460
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5527119
- 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
- gold
- doi.org
- 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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