ArticleThe Journal of clinical investigation1999
IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03149796 (The Effect of Tocilizumab), which is not on this map. Cited by 656 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effect of Tocilizumab (Anti-interleukin-6) Treatment on microRNA Expression and Adipokine Levels in Rheumatoid Arthritis Patients
Who cites it
656 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,678 citations in OpenAlex.
- Osteonecrosis as a manifestation of Long-COVID Syndrome: a systematic review.Musculoskeletal surgery · 2025Pooled it
- Unravelling the link between chronic inflammation and primary hyperparathyroidism: a systematic review.Frontiers in immunology · 2025Pooled it
- Changes in biomarkers levels from gingival crevicular fluid in pre- and postmenopausal women undergoing orthodontic treatment : A systematic review.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2024Pooled it
- Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis.The Journal of international medical research · 2021Pooled it
- Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials.Clinical rheumatology · 2019Pooled it
- General View of Arachidonic Acid (AA) Metabolism.Reviews of physiology, biochemistry and pharmacology · 2027Review
- β-Eudesmol Alleviates Inflammatory Injury in Septic Cardiomyopathy Through Enhancing GSK3B Activity to Inhibiting IL-17-Mediated Chemokine Expression.Biochemical genetics · 2026Article
- Precision immunopharmacology in peri-implantitis management: from molecular mechanisms to advanced therapeutic strategies.Frontiers in immunology · 2026Review
- Inflammatory cytokines mediate the common genetic and immunological background between rheumatoid arthritis and osteoporosis.Clinical rheumatology · 2026Article
- Fueling bone loss: the immunometabolic reprogramming of the bone microenvironment in diabetic osteoporosis.Frontiers in immunology · 2026Review
- Osteoimmunology: interactions of the bone and immune system.Frontiers in immunology · 2026Review
- Multi-system Mechanisms in the Anti-osteoporotic Effects of Herbal Natural Products.Endocrine, metabolic & immune disorders drug targets · 2026Review
- SAPHO syndrome and pustular skin diseases: shared inflammatory circuits, divergent tissue outcomes, and the limits of a spectrum model.Frontiers in immunology · 2026Review
- Brain-bone axis dysregulation: Biological code underlying the bidirectional association between depression and musculoskeletal disorders.Journal of orthopaedic translation · 2026Review
- Circadian rhythms regulate osteoclast recycling through gut microbiota-dependent Th17 cell expansion.Current research in microbial sciences · 2026Article
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.Biochemistry and biophysics reports · 2025Review
- TScience immunology · 2025Article
- Review
- Defining the Tumor-Bone axis: the role of extracellular vesicles in a crucial exchange route for breast cancer development and progression.Clinical & experimental metastasis · 2025Review
596 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-17 is a newly discovered T cell-derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17-induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti-IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.