Cited by 1,636Bone Metabolism and DiseasesOsteomyelitis and Bone Disorders ResearchRheumatoid Arthritis Research and Therapies

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.

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Hsu, Hailing, Lacey, David L., Dunstan, Colin R., Solovyev, Irina, Colombero, Anne, Timms, Emma, Tan, Hong-Lin, Elliott, Gary +13 more·1999·Proceedings of the National Academy of Sciences

Abstract

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo . Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo . Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.

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Crossref · 10.1073/pnas.96.7.3540

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Authors
Hsu, H., Lacey, D. L., Dunstan, C. R., Solovyev, I., Colombero, A., Timms, E., Tan, H.-L., Elliott, G., Kelley, M. J., Sarosi, I., Wang, L., Xia, X.-Z., Elliott, R., Chiu, L., Black, T., Scully, S., Capparelli, C., Morony, S., Shimamoto, G., Bass, M. B., & Boyle, W. J.
Affiliations
Amgen (United States) (US)
Venue
Proceedings of the National Academy of Sciences
Published
1999-03-30
Volume
96
Issue
7
Pages
3540-3545
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2106766464
Cited by
1,636
References
22
Citations by year
2026: 14 · 2025: 18 · 2024: 21 · 2023: 27 · 2022: 34 · 2021: 31 · 2020: 46 · 2019: 51 · 2018: 50 · 2017: 41 · 2016: 35 · 2015: 53 · 2014: 64 · 2013: 67 · 2012: 79
FWCI
25.42
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
RANK, osteoprotegerin ligand, osteoclastogenesis, osteoclast activation, TNF receptor superfamily, osteopetrosis, RANK signaling
MeSH terms
Animals, Bone Development, Carrier Proteins, Cell Differentiation, Cell Line, Cloning, Molecular, Glycoproteins, Humans, Immunoglobulin G, Male, Membrane Glycoproteins, Mice, Inbred Strains, Mice, Transgenic, Osteoclasts, Osteogenesis, Recombinant Fusion Proteins, Recombinant Proteins, Transcription, Genetic, Transfection, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Gene Expression Regulation, Developmental, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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