Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis.

Crotti, T N; Smith, M D; Weedon, H; Ahern, M J; Findlay, D M; Kraan, M; Tak, P P; Haynes, D R

doi:10.1136/ard.61.12.1047

Cited by 186Rheumatoid Arthritis Research and TherapiesNatural Compounds in Disease TreatmentNF-κB Signaling Pathways

Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis.

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Crotti, T N, Smith, M D, Weedon, H, Ahern, M J, Findlay, D M, Kraan, M, Tak, P P, Haynes, D R·2002·Annals of the Rheumatic Diseases

DOI 10.1136/ard.61.12.1047

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Abstract

Objectives To compare receptor activator of NF-kappaB ligand (RANKL) production in the synovial tissue from patients with active rheumatoid arthritis (RA), inactive RA, spondyloarthropathies (SpA), osteoarthritis, and from normal subjects. In addition, to establish the cell lineages expressing RANKL in these tissues.Methods Immunohistological analysis of frozen synovial tissue biopsy specimens was performed using a monoclonal antibody (mAb) to detect RANKL. Sections were evaluated by computer assisted image analysis and semiquantitative analysis to compare RANKL expression between groups. Dual and sequential labelling with mAb RANKL and cell lineage specific monoclonal antibodies were used to determine the types of cells expressing RANKL.Results Higher levels of RANKL were expressed in tissues from patients with active RA and SpA than in tissues from patients with inactive RA, osteoarthritis, and from normal subjects. RANKL protein was associated with CD3 antigen-positive lymphocytes and some macrophages. RANKL was predominantly associated with activated, memory T cells (CD45Ro positive cells) in patients with active RA and spondyloarthropathy (SpA).Conclusions The highest levels of RANKL were detected in patients with RA with active synovitis and in some patients with SpA. An increase in RANKL in the inflamed joint of patients with RA, produced by infiltrating activated T cells and macrophages, is likely to be an important cause of joint erosions in RA.

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Both T cells and non-T cells are sources of RANKL in the synovium.
“Both T cells and non-T cells have been observed to be the source of RANKL in the synovium (413, 418).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [413]
Synovial cells taken from rheumatoid joints express RANKL, RANK, and OPG.
“Synovial cells isolated from rheumatoid joints have been found to express RANKL, RANK, and OPG (90, 412-415).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [413]
Activated T lymphocytes in arthritic joints express RANKL.
“Activated T lymphocytes within arthritic joints have also been shown to express RANKL and therefore might contribute to the promotion of bone erosions (413, 416).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [413]
RANKL expression is higher in synovial tissue from active RA patients than in tissue from patients with quiescent disease.
“Higher levels of RANKL expression have been observed in synovial tissue from active RA patients vs. those with quiescent disease (413).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [413]
Activated T lymphocytes in arthritic joints may contribute to bone erosions.
“Activated T lymphocytes within arthritic joints have also been shown to express RANKL and therefore might contribute to the promotion of bone erosions (413, 416).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [413]

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Authors: Crotti, T. N., Smith, M. D., Weedon, H., Ahern, M. J., Findlay, D. M., Kraan, M., Tak, P. P., & Haynes, D. R.
Affiliations: The University of Adelaide (AU)
Repatriation General Hospital (AU)
Flinders University (AU)
Corresponding author: Haynes, D R
ORCID: Crotti, T N
Smith, M D
Ahern, M J
Findlay, D M
Kraan, M
Tak, P P
Haynes, D R
Venue: Annals of the Rheumatic Diseases
Publisher: Elsevier BV
Published: 2002-12
Volume: 61
Issue: 12
Pages: 1047-1054
ISSN: 0003-4967 (ISSN-L)
DOI: 10.1136/ard.61.12.1047
OpenAlex: W2148172224
Cited by: 186
References: 50
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 15
FWCI: 5.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Annals of the Rheumatic Diseases (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed (publishedVersion)
UvA-DARE (University of Amsterdam) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: Flinders University
Medical Research Council
National Health and Medical Research Council
Topics: Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: RANKL, rheumatoid arthritis, spondyloarthritis, osteoarthritis, synovium, synovitis, activated T cells, memory T cells, CD3+ T cells, macrophages, joint erosions, disease activity
MeSH terms: Adult, Aged, Arthritis, Rheumatoid, Female, Glycoproteins, Humans, Immunoenzyme Techniques, Leukocytes, Mononuclear, Lymphocytes, Macrophages, Male, Middle Aged, Osteoarthritis, Synovial Fluid, CD3 Complex, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Spondylarthropathies, Osteoprotegerin

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Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis.

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