ArticleThe Journal of clinical investigation2007
IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
242 citing papers in PubMed, 1 synthesis or guideline pooled it, 452 citations in OpenAlex.
- Lipopolysaccharide-Induced Bone Loss in Rodent Models: A Systematic Review and Meta-Analysis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Pooled it
- Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study.PloS one · 2017Trial
- The dynamic landscape of T helper cell plasticity and Th17-Treg instability in periodontitis.Experimental & molecular medicine · 2026Review
- Cytokine Regulation of the Bone Pre- and Metastatic Niches: Implications for Breast Cancer Dormancy.Cells · 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
- Interplay between gut health, immunity, and bone development in broilers: role of feed additives.Poultry science · 2026Review
- Temporal immunomodulation of CD4Science advances · 2026Article
- A Bone-Protective Role for IFN-γ? Evidence from Genetic Association and Osteoblast Functional Assays in Postmenopausal Osteoporosis.International journal of molecular sciences · 2026Article
- OX40L in endothelial cells promotes temporomandibular joint subchondral bone angiogenesis and osteoclastogenesis in mice.Bone & joint research · 2026Article
- Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026Review
- Immune Checkpoint Inhibitors and Bone Health: Mechanisms, Clinical Implications, and Emerging Perspectives on Bone Fragility.Current osteoporosis reports · 2026Review
- Recent progress in immunomodulation-based strategies for bone repair.Regenerative therapy · 2026Review
- Bridging Osteoimmunology and Regenerative Therapy: The Role of MSCs and Extracellular Vesicles.International journal of molecular sciences · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- RANKL-convergent osteoimmune network framework in osteoporosis: integrating macrophage activation, T-cell imbalance, and cytokine crosstalk.Frontiers in immunology · 2026Review
- A synbiotic medical food improves gut barrier function, reduces immune responses, and inhibits osteoclast activity in models of postmenopausal bone loss aligned with clinical outcomes.Journal of functional foods · 2025Article
- Immune-Guided Bone Healing: The Role of Osteoimmunity in Tissue Engineering Approaches.International journal of molecular sciences · 2025Review
- Photobiomodulation Meets Mechanotransduction: Immune-Stromal Crosstalk in Orthodontic Remodeling.Biomedicines · 2025Review
- Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.Bone research · 2025Review
182 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
8 authors at 2 institutions in 2 countries.
Funding
Abstract
T cell-produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-gamma is a major product of activated T helper cells that can function as a pro- or antiresorptive cytokine, but the reason why IFN-gamma has variable effects in bone is unknown. Here we show that IFN-gamma blunts osteoclast formation through direct targeting of osteoclast precursors but indirectly stimulates osteoclast formation and promotes bone resorption by stimulating antigen-dependent T cell activation and T cell secretion of the osteoclastogenic factors RANKL and TNF-alpha. Analysis of the in vivo effects of IFN-gamma in 3 mouse models of bone loss - ovariectomy, LPS injection, and inflammation via silencing of TGF-beta signaling in T cells - reveals that the net effect of IFN-gamma in these conditions is that of stimulating bone resorption and bone loss. In summary, IFN-gamma has both direct anti-osteoclastogenic and indirect pro-osteoclastogenic properties in vivo. Under conditions of estrogen deficiency, infection, and inflammation, the net balance of these 2 opposing forces is biased toward bone resorption. Inhibition of IFN-gamma signaling may thus represent a novel strategy to simultaneously reduce inflammation and bone loss in common forms of osteoporosis.
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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.