The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-κB ligand.
Open accessAbstract
Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Western blot analysis, soluble RANKL was detected as two different molecular weight products, and RNA interference of MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular weight products. Suppression of MMP14 in primary osteoblasts increased membrane-bound RANKL and promoted osteoclastogenesis in cocultures with macrophages. Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly reduced, and their osteoclastogenic activity was promoted, consistent with the findings of increased osteoclastogenesis in vivo. RANKL shedding is an important process that down-regulates local osteoclastogenesis.
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“There are at least three forms of RANKL, two of which possess a transmembrane domain that positions the biologically active carboxy-terminus to the extracellular domain (i.e., a type II transmembrane protein) (Fig. 2).One of these forms, RANKL2, is a shorter alternative splicing variant of RANKL1 (44).Both of these variants can remain on cell surfaces or can be proteolytically cleaved into soluble”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [45]
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Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
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A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells
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Self-citationOsteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
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A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
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Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
Takayanagi, H. (2007) · Nature Reviews Immunology · doi:10.1038/nri2062 · Cited by 1,878
Functions of RANKL/RANK/OPG in bone modeling and remodeling
Boyce, B. F., & Xing, L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.03.018 · Cited by 1,844
Edwards, D. R., Handsley, M. M., & Pennington, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,163
Biology of RANK, RANKL, and osteoprotegerin
Boyce, B. F., & Xing, L. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2165 · Cited by 994
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Metadata
- Authors
- Hikita, A., Yana, I., Wakeyama, H., Nakamura, M., Kadono, Y., Oshima, Y., Nakamura, K., Seiki, M., & Tanaka, S.
- Affiliations
- The University of Tokyo (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Tanaka, Sakae
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 281
- Issue
- 48
- Pages
- 36846-36855
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1999201913
- Cited by
- 236
- References
- 41
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 15 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 8 · 2018: 13 · 2017: 17 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 12
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- RANKL, ectodomain shedding, osteoclastogenesis, MMP-14, ADAM10, soluble RANKL, osteoblasts
- MeSH terms
- ADAM10 Protein, Animals, Binding Sites, Bone Diseases, Metabolic, Bone Marrow, Humans, Macrophages, Membrane Proteins, Mice, Inbred C57BL, Osteoblasts, Osteoclasts, Down-Regulation, Coculture Techniques, Mice, ADAM Proteins, RANK Ligand, Matrix Metalloproteinase 14, Amyloid Precursor Protein Secretases
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