ArticlePloS one2016
HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- Gla Rich Protein (GRP) Mediates Vascular Smooth Muscle Cell (VSMC) Osteogenic Differentiation, Extracellular Vesicle (EV) Calcification Propensity, and Immunomodulatory Properties.International journal of molecular sciences · 2024Article
- A new perspective on intervertebral disc calcification-from bench to bedside.Bone research · 2024Review
- Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease.International journal of biological sciences · 2023Review
- Macrophage death in atherosclerosis: potential role in calcification.Frontiers in immunology · 2023Review
- Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy.International journal of molecular sciences · 2022Review
- Matrix Vesicles as a Therapeutic Target for Vascular Calcification.Frontiers in cell and developmental biology · 2022Review
- Extracellular Vesicles From LPS-Treated Macrophages Aggravate Smooth Muscle Cell Calcification by Propagating Inflammation and Oxidative Stress.Frontiers in cell and developmental biology · 2022Article
- Cellular Crosstalk in the Vascular Wall Microenvironment: The Role of Exosomes in Vascular Calcification.Frontiers in cardiovascular medicine · 2022Review
- P2X7 Purinoceptor Affects Ectopic Calcification of Dystrophic Muscles.Frontiers in pharmacology · 2022Article
- The Pulp Stones: Morphological Analysis in Scanning Electron Microscopy and Spectroscopic Chemical Quantification.Medicina (Kaunas, Lithuania) · 2021Article
- Article
- Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review
- Article
- Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging.Aging cell · 2020Article
- A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs.Biology · 2020Review
- Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection.Molecular brain · 2020Article
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous clinical conditions have been linked to ectopic mineralization (EM). This process of pathological biomineralization is complex and not fully elucidated, but thought to be started within matrix vesicles (MVs). We hypothesized that high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions, induces EM via promoting MVs secretion from macrophages. In this study, we found that HMGB1 significantly promoted secretion of MVs from macrophages and subsequently led to mineral deposition in elevated Ca/Pi medium in vitro. Transmission electron microscopy of calcifying MVs showed formation of hydroxyapatite crystals in the vesicle interior. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase2 (nSMase2) that involved the receptor for advanced glycation end products (RAGE) and p38 MAPK (upstream of nSMase2). Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. Collectively, HMGB1 induces MVs secretion from macrophages at least in part, via the RAGE/p38 MAPK/nSMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 induces ectopic mineralization.
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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.