ArticleScientific reports2017
Combination of IL-6 and sIL-6R differentially regulate varying levels of RANKL-induced osteoclastogenesis through NF-κB, ERK and JNK signaling pathways.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- BioBERT-powered synergy: advanced bibliometric and molecular insights into prostate cancer bone metastasis.Frontiers in immunology · 2025Pooled it
- S100A9 Induces RANKL Expression in Osteocytes Utilizing IL-6/sIL-6R Combination and gp130 Signaling Pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cellular senescence and the SASP in skeletal ageing: convergent mechanisms of progressive bone loss in osteoporosis.Biogerontology · 2026Review
- Human parvovirus B19 VP1u‑induced osteoclastogenesis is enhanced by RANKL in RAW264.7 macrophage cells.Molecular medicine reports · 2026Article
- Estradiol Enhances Alveolar Bone Resorption by Promoting Osteoclast Differentiation in Experimental Periodontitis.Dentistry journal · 2026Article
- Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026Review
- The Alamandine/MrgprD as a Key Player in Antiresorptive Effects in an Osteoporosis Experimental Model.Calcified tissue international · 2026Article
- In vitro characterization of osteoblasts from craniofacial fibrous dysplasia of bone and their impact on bone homeostasis.Orphanet journal of rare diseases · 2026Article
- Lymphatic vascular aging and age-related bone loss: current status and future perspectives.Frontiers in immunology · 2026Review
- Introduction to Oral Immunity.Advances in experimental medicine and biology · 2026Review
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- Beyond the bladder: Escherichia coli UTIs drive systemic inflammation and RANKL-mediated bone resorption.Irish journal of medical science · 2025Article
- Effectiveness of local Tocilizumab administration in mitigating alveolar bone loss and inflammation in experimental periodontitis.Scientific reports · 2025Article
- Combined protection against UVB-induced photoaging by oleuropein, hydroxytyrosol, and verbascoside through modulation of inflammation, oxidative stress, and collagen homeostasis.Scientific reports · 2025Article
- Blocking the IL‑6 pathway to treat immune checkpoint inhibitor‑induced inflammatory arthritis (Review).Molecular medicine reports · 2025Review
- Deciphering the role of ERK and PI3K/Akt as crosstalk pathways between fibroblast-like synoviocytes and osteoclasts; novel therapeutic approach for rheumatoid arthritis.Molecular biology reports · 2025Review
- Exercise-Mediated Skeletal Muscle-Derived IL-6 Regulates Bone Metabolism: A New Perspective on Muscle-Bone Crosstalk.Biomolecules · 2025Review
- Effects of endurance exercise and dietary protein intake on osteokine, bone turnover, and inflammatory markers in endurance runners: A narrative review.Bone reports · 2025Review
- Unravelling the role of interleukin-6 in regulating dental stem cell behaviour: a scoping review.BMC oral health · 2025Article
- Immune cell profiles and predictive modeling in osteoporotic vertebral fractures using XGBoost machine learning algorithms.BioData mining · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin (IL)-6 is known to indirectly enhance osteoclast formation by promoting receptor activator of nuclear factor kappa-B ligand (RANKL) production by osteoblastic/stromal cells. However, little is known about the direct effect of IL-6 on osteoclastogenesis. Here, we determined the direct effects of IL-6 and its soluble receptor (sIL-6R) on RANKL-induced osteoclast formation by osteoclast precursors in vitro. We found IL-6/sIL-6R significantly promoted and suppressed osteoclast differentiation induced by low- (10 ng/ml) and high-level (50 ng/ml) RANKL, respectively. Using a bone resorption pit formation assay, expression of osteoclastic marker genes and transcription factors confirmed differential regulation of RANKL-induced osteoclastogenesis by IL-6/sIL-6R. Intracellular signaling transduction analysis revealed IL-6/sIL-6R specifically upregulated and downregulated the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), ERK (extracellular signal-regulated kinase) and JNK (c-Jun N-terminal kinase) induced by low- and high level RANKL, respectively. Taken together, our findings demonstrate that IL-6/sIL-6R differentially regulate RANKL-induced osteoclast differentiation and activity through modulation of NF-κB, ERK and JNK signaling pathways. Thus, IL-6 likely plays a dual role in osteoclastogenesis either as a pro-resorption factor or as a protector of bone, depending on the level of RANKL within the local microenvironment.
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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.