Osteoprotegerin reduces the serum level of receptor activator of NF-κB ligand derived from osteoblasts.
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Osteoprotegerin (OPG) is a decoy receptor for receptor activator of NF-κB ligand (RANKL). We previously reported that OPG deficiency elevated the circulating level of RANKL in mice. Using OPG−/− mice, we investigated whether OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts and activated T cells in culture released a large amount of RANKL in the absence of OPG. OPG or a soluble form of receptor activator of NF-κB (the receptor of RANKL) suppressed the release of RANKL from those cells. OPG- and T cell-double-deficient mice showed an elevated serum RANKL level equivalent to that of OPG−/− mice, indicating that circulating RANKL is mainly derived from bone. The serum level of RANKL in OPG−/− mice was increased by ovariectomy or administration of 1α,25-dihydroxyvitamin D3. Expression of RANKL mRNA in bone, but not thymus or spleen, was increased in wild-type and OPG−/− mice by 1α,25-dihydroxyvitamin D3. These results suggest that OPG suppresses the shedding of RANKL from osteoblasts and that the serum RANKL in OPG−/− mice exactly reflects the state of bone resorption.
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Both soluble and membrane-bound forms of RANKL expressed by T cells are implicated in focal bone erosions in inflammatory arthritis.
“T Cells express both soluble and membrane-bound forms of RANKL (49,50), and both forms are implicated in focal bone erosions associated with inflammatory arthritis (26,49).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [50]
OVX increases RANKL levels in various animal models.
“OVX has been shown to increase RANKL levels in various animal models (50, 198 -201).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [50]
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Makrygiannakis, D. (2008) · Figshare
et cible thérapeutique dans l'ostéoporose
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Sari, G. M., Soetjipto, S., & Herawati, L. (2020) · Universitas Airlangga Repository (Universitas Airlangga)
Bone remodeling during alveolar repair is impaired by RANKL antagonist
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Role of osteoblast-lineage cells in the systemic control of breast cancer growth and metastasis
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- Authors
- Nakamichi, Y., Udagawa, N., Kobayashi, Y., Nakamura, M., Yamamoto, Y., Yamashita, T., Mizoguchi, T., Sato, M., Mogi, M., Penninger, J. M., & Takahashi, N.
- Affiliations
- Matsumoto Dental University (JP)
- Aichi Gakuin University (JP)
- Institute of Molecular Biotechnology (AT)
- Corresponding author
- Nakamichi, Yuko
- Kobayashi, Yasuhiro
- Yamashita, Teruhito
- Mizoguchi, Toshihide
- Takahashi, Naoyuki
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-01
- Volume
- 178
- Issue
- 1
- Pages
- 192-200
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1536343809
- Cited by
- 50
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2017: 3 · 2016: 5 · 2015: 1 · 2013: 3 · 2012: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (16390535, 17390497)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoprotegerin, RANKL, RANK, osteoblasts, bone resorption, activated T cells, 1,25-dihydroxyvitamin D3, ovariectomy
- MeSH terms
- ADAM17 Protein, Animals, Bone Resorption, Calcitriol, Ligands, Mice, Mutant Strains, Osteoblasts, RNA, Messenger, Spleen, T-Lymphocytes, Thymus Gland, NF-kappa B, Mice, ADAM Proteins, Osteoprotegerin, RANK Ligand, Matrix Metalloproteinases, Membrane-Associated
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