ArticleCell death & disease2022
Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Pooled it
- Spatial multi‑omics identifies an SPP1+ macrophage‑driven anti‑apoptotic niche in osteoarthritis synovium via the SPP1‑CD44 axis.International journal of molecular medicine · 2026Article
- Integrated analysis of single-cell RNA sequencing, transcriptomics, and thermal proteome profiling identifies PLCG1 as the therapeutic target of isopimpinellin in treating rheumatoid arthritis.Cellular & molecular biology letters · 2026Article
- Integrating multi-omics, machine learning, and molecular dynamics simulations to identify glutamate metabolism-related biomarkers and drug candidates in rheumatoid arthritis.Frontiers in molecular biosciences · 2026Article
- Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential.Frontiers in immunology · 2026Review
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- Hydrogel delivering self-assembled herbal nanoparticles accelerates diabetic wound healing through mitochondrial regulation.Materials today. Bio · 2025Article
- Glucose tasting depletes intracellular calcium stores and impairs macrophage functionality.iScience · 2025Article
- The Salmonella pathogenicity island 1 injectisome reprograms host cell translation to evade the inflammatory response.Nature communications · 2025Article
- Review
- Hair Calcium Levels in Relation to Coronary Artery Disease Severity and Systemic Inflammation Markers: A Pilot Study.Journal of clinical medicine · 2025Article
- The formation and function of calciprotein particles.Pflugers Archiv : European journal of physiology · 2025Review
- New Cardiovascular Risk Biomarkers in Rheumatoid Arthritis: Implications and Clinical Utility-A Narrative Review.Biomedicines · 2025Review
- SPP1 macrophages across diseases: A call for reclassification?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Relationship between SPP1 (Osteopontin) and extracellular matrix dynamics: a comprehensive review.Frontiers in medicine · 2025Review
- Single-Cell Analysis Reveals the Cellular and Molecular Changes of Liver Injury and Fibrosis in Mice During the Progression ofCurrent issues in molecular biology · 2024Article
- Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality.Journal of neural engineering · 2024Article
- [Exploring the mechanism of IgA vasculitis pathogenesis through the interaction of thrombin and inflammatory factors using urinary proteomics].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- Anti-inflammatory and immunoregulatory effects of colistin sulphate on human PBMCs.Journal of cellular and molecular medicine · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The danger signal extracellular calcium is pathophysiologically increased in the synovial fluid of patients with rheumatoid arthritis (RA). Calcium activates the NLRP3-inflammasome via the calcium-sensing receptor in monocytes/macrophages primed by lipopolysaccharide, and this effect is mediated by the uptake of calciprotein particles (CPPs) formed out of calcium, phosphate, and fetuin-A. Aim of the study was to unravel the influence of calcium on monocytes when the priming signal is not present. Monocytes were isolated from the blood of healthy controls and RA patients. Macrophages were characterized using scRNA-seq, DNA microarray, and proteomics. Imaging flow cytometry was utilized to study intracellular events. Here we show that extracellular calcium and CPPs lead to the differentiation of monocytes into calcium-macrophages when the priming signal is absent. Additional growth factors are not needed, and differentiation is triggered by calcium-dependent CPP-uptake, lysosomal alkalization due to CPP overload, and TFEB- and STAT3-dependent increased transcription of the lysosomal gene network. Calcium-macrophages have a needle-like shape, are characterized by excessive, constitutive SPP1/osteopontin production and a strong pro-inflammatory cytokine response. Calcium-macrophages differentiated out of RA monocytes show a stronger manifestation of this phenotype, suggesting the differentiation process might lead to the pro-inflammatory macrophage response seen in the RA synovial membrane.
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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.