ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2012
Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026Review
- Decoding the secretory blueprint of bone healing: from gradients to regeneration.Frontiers in cell and developmental biology · 2026Review
- Rewiring osteoimmune homeostasis in osteoporosis: T-cell subsets as key regulators and emerging therapeutic targets.Frontiers in immunology · 2026Review
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- IFNγ production during cell interactions distinguishes localized from diffuse pigmented villonodular synovitis and rheumatoid arthritis.Arthritis research & therapy · 2025Article
- Osteoimmunology: Crosstalk Between T Cells and Osteoclasts in Osteoporosis.Clinical reviews in allergy & immunology · 2025Review
- Chamomile Tincture and Lidocaine Hydrochloride Gel Ameliorates Periodontitis: A Preclinical Study.Biomedicines · 2024Article
- Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology.Frontiers in immunology · 2024Review
- Inflamm-Aging-Related Cytokines of IL-17 and IFN-Journal of immunology research · 2021Article
- The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence.International journal of molecular sciences · 2019Review
- Interferon-Gamma-Mediated Osteoimmunology.Frontiers in immunology · 2018Review
- Interferon-γ Released by Activated CD8The American journal of pathology · 2017Article
- Abrasive Endoprosthetic Wear Particles Inhibit IFN-γ Secretion in Human Monocytes Via Upregulating TNF-α-Induced miR-29b.Inflammation · 2017Article
- The effects of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in osteopenia women.Journal of exercise nutrition & biochemistry · 2014Article
- Molecular mechanism of thiazolidinedione-mediated inhibitory effects on osteoclastogenesis.PloS one · 2014Article
- Osteoclasts: New Insights.Bone research · 2013Review
- Pathways for bone loss in inflammatory disease.Current osteoporosis reports · 2012Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although interferon-γ (IFN-γ) potently inhibits osteoclastogenesis, the suppressive effect is significantly reduced when osteoclast precursors are pre-exposed to the receptor activator of NF-κB (RANK) ligand (RANKL). However, the molecular mechanism underlying the biphasic effects of IFN-γ on osteoclastogenesis remains elusive. Here, we recapitulate the biphasic functions of IFN-γ in osteoclastogenesis in both tissue culture dishes and on bone slices. We further demonstrate that IFN-γ markedly suppresses the RANKL-induced expression of nuclear factor of activated T-cells c1 (NFATc1) in normal, but not RANKL-pretreated bone marrow macrophages (BMMs). Similarly, IFN-γ impairs the activation of the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways in normal, but not RANKL-pretreated, BMMs. These findings indicate that IFN-γ inhibits osteoclastogenesis partially by suppressing the expression of NFATc1 and the activation of the NF-κB and JNK pathways. Moreover, IFN-γ inhibits the RANKL-induced expression of osteoclast genes, but RANKL pretreatment reprograms osteoclast genes into a state in which they can no longer be suppressed by IFN-γ, indicating that IFN-γ inhibits osteoclastogenesis by blocking the expression of osteoclast genes. Finally, the IVVY(535-538) motif in the cytoplasmic domain of RANK is responsible for rendering BMMs refractory to the inhibitory effect of IFN-γ. Taken together, these findings provide important mechanistic insights into the biphasic effects of IFN-γ on osteoclastogenesis.
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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.