ArticleCell reports2014
Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Interleukin-9 Facilitates Osteoclastogenesis in Rheumatoid Arthritis.International journal of molecular sciences · 2021Trial
- Ion channel/Stat6-driven nano-immune programming of tissue-resident macrophages by amide-functionalized nanocellulose.Bioactive materials · 2026Article
- Synovial transcriptional clusters link cartilage degeneration to cell-type-specific gene expression in knee osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Fluorescence-Guided Spatial Mapping of p21-Expressing Senescent Cells in Aged Liver at Single-Cell Resolution.Biomolecules · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Host- and genotype-specific transcriptomic responses toFrontiers in immunology · 2026Article
- Integrating network toxicology and in vitro validation to elucidate PET microplastic-induced osteoarthritis pathogenesis.Frontiers in pharmacology · 2026Article
- Unveiling the link between lactate metabolism and rheumatoid arthritis through integration of bioinformatics and machine learning.Scientific reports · 2024Article
- Bone Trans-omics: Integrating Omics to Unveil Mechanistic Molecular Networks Regulating Bone Biology and Disease.Current osteoporosis reports · 2023Review
- Article
- Multinucleation resets human macrophages for specialized functions at the expense of their identity.EMBO reports · 2023Article
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- Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis.Frontiers in immunology · 2022Review
- Blockade of SK4 channels suppresses atrial fibrillation by attenuating atrial fibrosis in canines with prolonged atrial pacing.International journal of medical sciences · 2022Article
- Adipoclast: a multinucleated fat-eating macrophage.BMC biology · 2021Review
- Using "-omics" Data to Inform Genome-wide Association Studies (GWASs) in the Osteoporosis Field.Current osteoporosis reports · 2021Review
- Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients.Journal of clinical medicine · 2021Article
- KCa3.1 Inhibition of Macrophages Suppresses Inflammatory Response Leading to Endothelial Damage in a Cell Model of Kawasaki Disease.Journal of inflammation research · 2021Article
- BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages.Journal of cell science · 2020Article
- Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity-Potential Implications for Drug Sensitivity.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 2 countries.
Funding
Abstract
Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation.
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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.