Osteoprotegerin: Multiple partners for multiple functions
Abstract
Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation. However, there are additional ligands of OPG that confer various biological functions. OPG can promote cell survival, cell proliferation and facilitates migration by binding TNF-related apoptosis inducing ligand (TRAIL), glycosaminoglycans or proteoglycans. A large number of in vitro, pre-clinical and clinical studies provide evidences of OPG involvement in vascular, bone, immune and tumor biology. This review describes an overview of the different OPG ligands regulating its biological functions.
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Increased RANK signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.
“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [35]
The citation is attached to the premise about osteoclast differentiation and survival; the ACVR2B/Fc mechanism is the citing authors’ own inference. In “RANKL and TRAIL: ligands from the TNF family” (page unavailable), the source says RANKL–RANK signaling regulates osteoclast differentiation and survival, but it does not establish the same role for TRAIL. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTRAIL and RANKL are known to regulate osteoclast differentiation and survival.
“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [35]
In “RANKL and TRAIL: ligands from the TNF family” (page unavailable), the paper says RANKL–RANK signaling is involved in osteoclast differentiation and survival. It discusses TRAIL-induced apoptosis in other cell types, but does not say TRAIL regulates osteoclast differentiation or survival. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Osteoprotegerin deficiency leads to deformation of the articular cartilage in femoral head
Liu, Y., Ge, J., Chen, D., Weng, Y., Du, H., Sun, Y., & Zhang, Q. (2016) · Journal of Molecular Histology · doi:10.1007/s10735-016-9689-9 · Cited by 9 · see citing works
Cystathionine gamma lyase aggravates orthodontic root resorption in mice
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RANK/RANKL Signaling Pathway in Breast Development and Cancer
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The mechanism of bone metabolism in a Sprague Dawley rat model of mandibular osteoradionecrosis
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- Authors
- Baud’huin, M., Duplomb, L., Teletchea, S., Lamoureux, F., Ruiz-Velasco, C., Maillasson, M., Redini, F., Heymann, M.-F., & Heymann, D.
- Affiliations
- Inserm (FR)
- Université de Bourgogne (FR)
- Corresponding author
- Baud’huin, Marc
- Heymann, Dominique
- ORCID
- Venue
- Cytokine & Growth Factor Reviews
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 24
- Issue
- 5
- Pages
- 401-409
- ISSN
- 1359-6101 (ISSN-L)
- OpenAlex
- W2032215600
- Cited by
- 153
- References
- 85
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 14 · 2023: 14 · 2022: 12 · 2021: 11 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 10 · 2016: 21 · 2015: 16 · 2014: 9 · 2013: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine & Growth Factor Reviews (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- osteoprotegerin, RANKL, TRAIL, glycosaminoglycans, proteoglycans, osteoclastogenesis, bone turnover, cell survival, cell proliferation, cell migration, vascular biology, tumor biology
- MeSH terms
- Animals, Cell Differentiation, Cell Survival, Humans, Osteoclasts, Cell Proliferation, TNF-Related Apoptosis-Inducing Ligand, Osteoprotegerin, RANK Ligand
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