ArticleArthritis & rheumatology (Hoboken, N.J.)2016
RANK-Independent Osteoclast Formation and Bone Erosion in Inflammatory Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 142 citations in OpenAlex.
- Predicting the risk of bone erosion in rheumatoid arthritis using a SHAP-based interpretable machine learning model.Clinical rheumatology · 2026Article
- Punicalagin with anti-inflammatory activities affects Brd-4 mediated chromatin remodeling for attenuating inflammatory osteolysis.Scientific reports · 2026Article
- [Research progress on external cervical resorption].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Distinct osteoclastogenic potential of granulocyte-macrophage colony-stimulating factor-induced monocyte subsets.Bone reports · 2025Article
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
- Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multi-omics and network pharmacology reveal Huayu-Tongbi decoction reduced arthritis-related bone erosion.Chinese medicine · 2025Article
- IgG promotes TNF-α induced osteoclastogenesis by upregulating the expression of TNFR1 and the NF-κB signalling pathway.Clinical & translational immunology · 2025Article
- Macrophages and osteoclasts: similarity and divergence between bone phagocytes.Frontiers in immunology · 2025Review
- From death to birth: how osteocyte death promotes osteoclast formation.Frontiers in immunology · 2025Review
- Immunometabolic reprogramming in diabetic osteomyelitis: from mechanisms to therapeutics.Frontiers in cellular and infection microbiology · 2025Review
- Beyond inflammation: the molecular basis of bone remodeling in axial spondyloarthritis and psoriatic arthritis.Frontiers in immunology · 2025Review
- Investigating the protective effect of loganin in ovariectomy‑induced bone loss through network pharmacology and molecular docking.Experimental and therapeutic medicine · 2024Article
- Article
- Single-cell multi-omics identify novel regulators required for osteoclastogenesis during aging.iScience · 2024Article
- The miR-29-3p family suppresses inflammatory osteolysis.Journal of cellular physiology · 2024Article
- Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis-Mechanisms, Evidence, and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2024Review
- New Horizons: Translational Aspects of Osteomorphs.The Journal of clinical endocrinology and metabolism · 2024Review
- Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveProinflammatory molecules promote osteoclast-mediated bone erosion by up-regulating local RANKL production. However, recent evidence suggests that combinations of cytokines, such as tumor necrosis factor (TNF) plus interleukin-6 (IL-6), induce RANKL-independent osteoclastogenesis. The purpose of this study was to better understand TNF/IL-6-induced osteoclast formation and to determine whether RANK is absolutely required for osteoclastogenesis and bone erosion in murine inflammatory arthritis.
methodsMyeloid precursors from wild-type (WT) mice or mice with either germline or conditional deletion of Rank, Nfatc1, Dap12, or Fcrg were treated with either RANKL or TNF plus IL-6. Osteoprotegerin, anti-IL-6 receptor (anti-IL-6R), and hydroxyurea were used to block RANKL, the IL-6R, and cell proliferation, respectively. Clinical scoring, histologic assessment, micro-computed tomography, and quantitative polymerase chain reaction (qPCR) were used to evaluate K/BxN serum-transfer arthritis in WT and RANK-deleted mice. Loss of Rank was verified by qPCR and by osteoclast cultures.
resultsTNF/IL-6 generated osteoclasts in vitro that resorbed mineralized tissue through a pathway dependent on IL-6R, NFATc1, DNAX-activation protein 12, and cell proliferation, but independent of RANKL or RANK. Bone erosion and osteoclast formation were reduced, but not absent, in arthritic mice with inducible deficiency of RANK. TNF/IL-6, but not RANKL, induced osteoclast formation in bone marrow and synovial cultures from animals deficient in Rank. Multiple IL-6 family members (IL-6, leukemia inhibitory factor, oncostatin M) were up-regulated in the synovium of arthritic mice.
conclusionThe persistence of bone erosion and synovial osteoclasts in Rank-deficient mice, and the ability of TNF/IL-6 to induce osteoclastogenesis, suggest that more than one cytokine pathway exists to generate these bone-resorbing cells in inflamed joints.
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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.