ArticleBone2019
IL-6 and sIL-6R induces STAT3-dependent differentiation of human VSMCs into osteoblast-like cells through JMJD2B-mediated histone demethylation of RUNX2.
Article in Bone, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Risk factors for coronary artery calcification in Chinese patients undergoing maintenance hemodialysis: a meta-analysis.International urology and nephrology · 2025Pooled it
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- LNGFR promoting osteogenic differentiation of ectomesenchyme stem cells via activation of GHR-JAK-STAT/IGF1 signaling pathway.Stem cell research & therapy · 2026Article
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- Clostridium butyricum Promotes Bone Remodeling by Activating Inflammatory Genes in Mice.Probiotics and antimicrobial proteins · 2026Article
- Decoding vascular calcification: mechanistic insights and translational strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Foam cells: tracing the diverse cellular origins and their linked signaling pathways.Journal of translational medicine · 2025Review
- KDM4B modulates ERα signaling pathway to participate in vascular smooth muscle cell calcification.Cell death discovery · 2025Article
- Review of Promising Off-Label Use of Deucravacitinib.International journal of molecular sciences · 2025Review
- Distinct inflammatory pathways shape atherosclerosis in different vascular beds.European heart journal · 2025Review
- Mechanism of influence of calcified nanoparticles in the development of calcified diseases (Review).Biomedical reports · 2025Review
- Review
- Review
- Activation and targetability of TYMP-IL-6-TF signaling in the skin microenvironment in uremic calciphylaxis.Science translational medicine · 2025Article
- Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells.Acta pharmaceutica Sinica. B · 2025Article
- Repair mechanisms of bone system tissues based on comprehensive perspective of multi-omics.Cell biology and toxicology · 2025Review
- The association between frailty index and abdominal aortic calcification in the middle-aged and older US adults: NHANES 2013-2014.Frontiers in public health · 2025Article
- Oxidative stress and its related epigenetic modifications in vascular calcification: mechanisms and advances.Frontiers in cardiovascular medicine · 2025Review
- Fracture-Induced Immunological Cascades Trigger Rapid Systemic Bone Loss via Osteocyte-Regulated Osteoclastogenesis.ImmunoTargets and therapy · 2025Article
- Diabetes and calcific aortic valve disease: controversy of clinical outcomes in diabetes after aortic valve replacement.Frontiers in endocrinology · 2025Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation and vascular calcification are independent risk factors of cardiovascular events. Vascular smooth muscle cells (VSMCs) exhibit osteoblast-like characteristics in response to various stimuli such as oxidized cholesterol and inflammation. However the precise mechanism of transcriptional regulation of VSMCs by inflammatory stimuli remains unclear. We investigated the process and mechanisms of inflammatory cytokine-induced transformation of human VSMCs (hVSMCs) into osteoblast-like cells, with a special focus on epigenetic changes. Our results demonstrated: (1) interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) induced transformation of hVSMCs into an osteoblast phenotype, with subsequent vascular calcification, based on the results of Alizarin Red S staining and O-Cresolphthalein complexone method; (2) IL-6/sIL-6R accelerated the expression of runt-related transcription factor 2 (RUNX2) based on the results of quantitative real-time polymerase chain reaction; (3) Knockdown of signal transducer and activator of transcription (STAT) 3 reduced IL-6/sIL-6R-induced RUNX2 mRNA expression and osteoblast transdifferentiation of hVSMCs; (4) Chromatin immunoprecipitation (ChIP) coupled with PCR (ChIP-PCR) identified a STAT-binding site in RUNX2 promoter region containing trimethylated histone 3 lysine 9 (H3K9me3), a transcriptional repressor, and H3K4me3, a transcriptional enhancer. Stimulation with IL-6/sIL-6R suppressed H3K9me3 but not H3K4me3 through the recruitment of jumonji domain-containing protein (JMJD) 2B, a histone lysine demethylase, at the STAT-binding site in RUNX2 promoter region; (5) IL-6/sIL-6R-induced RUNX2 gene expression was inhibited in hVSMCs pretreated with JIB04, JMJD2 inhibitor, and the inhibitory effect was JIB04 dose-dependent. Our results indicate that the IL-6/STAT3/JMJD2B pathway regulates hVSMCs differentiation into osteoblast-like cells, which suggest its pathogenic role in vascular calcification associated with 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.