ArticleThe Journal of clinical investigation2000
TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 641 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
641 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,412 citations in OpenAlex.
- Protective effects and mechanisms of puerarin in ovariectomized animal models of osteoporosis: a systematic review and meta-analysis of preclinical studies.Frontiers in physiology · 2026Pooled it
- Alterations in bone fracture healing associated with TNFRSF signaling pathways.Frontiers in pharmacology · 2022Pooled it
- Interleukin-9 Facilitates Osteoclastogenesis in Rheumatoid Arthritis.International journal of molecular sciences · 2021Trial
- Sex Steroid Hormone Regulation of T-Cell Function and Antitumor Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Article
- LPS-Induced TNF-α and IL-1 Signaling in Periodontitis: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- The cortical microenvironment drives early immune organization and controls early osteoclastogenesis in bone healing.Nature communications · 2026Article
- Heme Oxygenase-1 in Bone Remodeling: Molecular Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Multifactorial Regulation of Inflammatory Bone Loss in Chronic Inflammatory and Immune-Associated Disorders: Osteoimmune Mechanisms and Translational Prospects of Natural Small Molecules.Calcified tissue international · 2026Review
- TLR4-dependent upregulation of IL-22-producing T cells in the bone niche links to the imbalance of bone homeostasis.Cellular & molecular biology letters · 2026Article
- Temporal immunomodulation of CD4Science advances · 2026Article
- Liraglutide, a GLP-1 Receptor Agonist, Mitigates LPS-Induced Osteoclastogenesis and Bone Loss by Downregulating Macrophage TNF-α Expression.International journal of molecular sciences · 2026Article
- Low-Intensity Pulsed Ultrasound Enhances Intramembranous Bone Healing in a Critical-Size Bone Defect of the Rat Calvaria.Journal of clinical medicine · 2026Article
- Cytokines as Key Drivers of Pathological Root Resorption: Integrating Molecular Mechanisms, Genetic Determinants, and Biomarker-Based Insights.Biomedicines · 2026Review
- Bacterial specificity of the gut microbiome predicts bone density in primary hyperparathyroidism.Bone research · 2026Article
- Osteoimmunology: Can We Prevent Bone Loss in Rheumatoid Arthritis with Modern Antirheumatic Drugs?Calcified tissue international · 2026Review
- Apoptotic extracellular vesicles act as master regulators of the bone healing niche.Journal of nanobiotechnology · 2026Review
- EBV promotes alveolar trabecula resorption via extracellular vesicle remodeling by group IIA secreted phospholipase AJournal of lipid research · 2026Article
- Article
- Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications to Promote Osteoclastogenesis.Biology · 2026Article
581 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
While TNF-alpha is pivotal to the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are unknown. We find that a pure population of murine osteoclast precursors fails to undergo osteoclastogenesis when treated with TNF-alpha alone. In contrast, the cytokine dramatically stimulates differentiation in macrophages primed by less than one percent of the amount of RANKL (ligand for the receptor activator of NF-kappaB) required to induce osteoclast formation. Mirroring their synergistic effects on osteoclast differentiation, TNF-alpha and RANKL markedly potentiate NF-kappaB and stress-activated protein kinase/c-Jun NH(2)-terminal kinase activity, two signaling pathways essential for osteoclastogenesis. In vivo administration of TNF-alpha prompts robust osteoclast formation in chimeric animals in which ss-galactosidase positive, TNF-responsive macrophages develop within a TNF-nonresponsive stromal environment. Thus, while TNF-alpha alone does not induce osteoclastogenesis, it does so both in vitro and in vivo by directly targeting macrophages within a stromal environment that expresses permissive levels of RANKL. Given the minuscule amount of RANKL sufficient to synergize with TNF-alpha to promote osteoclastogenesis, TNF-alpha appears to be a more convenient target in arresting inflammatory osteolysis.
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What OpenQuestion holds
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.