ArticleCardiovascular research2016
Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Pooled it
- Molecular Interactions Between Vascular Smooth Muscle Cells and Macrophages in Atherosclerosis.Frontiers in cardiovascular medicine · 2021Pooled it
- Review
- Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk.Nature communications · 2026Article
- The m6A reader YTHDF2 protects vascular smooth muscle cells against the osteogenic differentiation through targeting Runx2.Renal failure · 2025Article
- Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.Cell communication and signaling : CCS · 2025Article
- Farnesyltransferase inhibitors decrease matrix-vesicle-mediated mineralization in SaOS-2 cells.Molecular biology reports · 2025Article
- Impact of Abdominal Aortic Calcification on Long-Term Outcome after Gastric Cancer Surgery: a Retrospective Study.Journal of gastrointestinal cancer · 2025Article
- Modelling Atherosclerotic Plaque Cap Mechanics: Microcalcifications Reduce Mechanical Properties in Mesenchymal Stromal Cell-Based Model.Advanced biology · 2025Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis.Cardiovascular research · 2024Article
- Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.Cardiovascular diabetology · 2024Article
- The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics.Basic research in cardiology · 2024Review
- Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness.Circulation research · 2024Article
- A new perspective on intervertebral disc calcification-from bench to bedside.Bone research · 2024Review
- NovelFrontiers in pharmacology · 2024Article
- Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux.Scientific reports · 2023Article
- Long non-coding RNA MALAT1 sponges miR-30c to promote the calcification of human vascular smooth muscle cells by regulating Runx2.Renal failure · 2023Article
- PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice.BMC cardiovascular disorders · 2023Article
- The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/β-Catenin and RANKL/RANK/OPG signaling pathways.Molecular biology reports · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsVascular smooth muscle cells (SMCs) are major precursors contributing to osteochondrogenesis and calcification in atherosclerosis. Runt-related transcription factor-2 (Runx2) has been found essential for SMC differentiation to an osteochondrogenic phenotype and subsequent calcification in vitro. A recent study using a conditional targeting allele that produced a truncated Runx2 protein in SMCs of ApoE-/- mice showed reduced vascular calcification, likely occurring via reduction of receptor activator of nuclear factor-κB ligand (RANKL), macrophage infiltration, and atherosclerotic lesion formation. Using an improved conditional Runx2 knockout mouse model, we have elucidated new roles for SMC-specific Runx2 in arterial intimal calcification (AIC) without effects on atherosclerotic lesion size. METHODS AND
resultsWe used an improved targeting construct to generate LDLr-/- mice with floxed-Runx2 alleles ( LDLr-/- :Runx2 f/f ) such that Cre-mediated recombination ( LDLr-/- :Runx2 ΔSM ) does not produce functional truncated Runx2 protein, thereby avoiding off-target effects. We found that both LDLr-/- :Runx2 f/f and LDLr-/- :Runx2 ΔSM mice fed with a high fat diet developed atherosclerosis. SMC-specific Runx2 deletion did not significantly reduce atherosclerotic lesion size, macrophage number, or expression of RANKL, MCP-1, and CCR2. However, it significantly reduced AIC by 50%. Mechanistically, Sox9 and type II collagen were unaltered in vessels of LDLr-/- :Runx2 ΔSM mice compared to LDLr-/- :Runx2 f/f counterparts, while type X collagen, MMP13 and the osteoblastic marker osteocalcin were significantly reduced.
conclusionsSMC autonomous Runx2 is required for SMC differentiation towards osteoblast-like cells, SMC-derived chondrocyte maturation and AIC in atherosclerotic mice. These effects were independent of systemic lipid metabolism, RANKL expression, macrophage infiltration, and atheromatous lesion progression.
Identifiers
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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.