ArticleCell stem cell2017
Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.
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Article in Cell stem cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70citing papers in PubMed
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Who cites it
70 citing papers in PubMed, 125 citations in OpenAlex.
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- Asparagine endopeptidase prompts breast cancer-related pericardial calcification by regulating IGF2 and integrin αvβ5.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- YAP-Induced Glycolysis Drives Fibroinflammation and Disrupts Fibroblast Fidelity.Circulation research · 2025Article
- Fibroblast-Specific Loss of TGF-β Signaling Mediates Lipomatous Metaplasia in the Infarcted Heart.Circulation · 2025Article
- Blocking nuclear receptor Nr4a3 unlocks the senescence barrier to promote direct cardiac reprogramming.Science advances · 2025Article
- Pharmacological targeting of the IL-17/neutrophil axis attenuates calcific deposits in rat models of calciphylaxis.The Journal of clinical investigation · 2025Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- The Pathologic Actions of Phosphate in CKD.Kidney360 · 2025Review
- Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts.Heliyon · 2025Article
- Retrospective Cardiac Gating with A Prototype Small-Animal X-ray Computed Tomograph.Journal of visualized experiments : JoVE · 2025Article
- Erroneous Differentiation of Tendon Stem/Progenitor Cells in the Pathogenesis of Tendinopathy: Current Evidence and Future Perspectives.Stem cell reviews and reports · 2025Review
- Targeting fibroblasts in pathological bone formation: mechanisms and treatments.Frontiers in cell and developmental biology · 2025Review
- Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review).Oncology letters · 2024Review
- Novel Quantification Protocol for Cardiovascular Calcification Progression Using Longitudinal MicroPET/MicroCT Images.Journal of visualized experiments : JoVE · 2024Article
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- Development and Biomedical Application of Non-Noble Metal Nanomaterials in SERS.Nanomaterials (Basel, Switzerland) · 2024Review
- Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions.Nature communications · 2024Article
- Integration mapping of cardiac fibroblast single-cell transcriptomes elucidates cellular principles of fibrosis in diverse pathologies.Science advances · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 1 country.
Indulekha C L PillaiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Shen LiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Milagros RomayCardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Departments of Human Genetics & Microbiology, Immunology, and Molecular Genetics, UCLA, CA 90095, USA.
Larry LamDepartment of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Yan LuDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Jie HuangDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Nathaniel DillardDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Marketa ZemanovaDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Liudmilla RubbiDepartment of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Yibin WangCardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Anesthesiology, UCLA, CA 90095, USA; Department of Physiology, UCLA, CA 90095, USA.
Jason LeeJonsson Comprehensive Cancer Center, UCLA, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine and Crump Institute for Molecular Imaging, UCLA, CA 90095, USA.
Ming XiaJonsson Comprehensive Cancer Center, UCLA, CA 90095, USA; Department of Materials Science & Engineering, School of Engineering, UCLA, CA 90095, USA.
Owen LiangJonsson Comprehensive Cancer Center, UCLA, CA 90095, USA; Department of Materials Science & Engineering, School of Engineering, UCLA, CA 90095, USA.
Ya-Hong XieJonsson Comprehensive Cancer Center, UCLA, CA 90095, USA; Department of Materials Science & Engineering, School of Engineering, UCLA, CA 90095, USA.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA.
Aldons J LusisDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Departments of Human Genetics & Microbiology, Immunology, and Molecular Genetics, UCLA, CA 90095, USA.
Arjun DebDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA 90095, USA; Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, School of Letters and Sciences, UCLA, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, CA 90095, USA; Molecular Biology Institute, UCLA, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, CA 90095, USA. Electronic address: adeb@mednet.ucla.edu.
University of Colorado Cancer Center · USUCLA Jonsson Comprehensive Cancer CenterUniversity of Colorado Denver · USBroad Center · USUniversity of California, Los Angeles · USUCLA Health · US
Funding
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2MSystems Approach to Unraveling the Genetic Basis of Heart FailureR01HL114437 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENG, MARIO C., KARMA, ALAIN S · 2013 to 2016
$4.7MEpigenomic Mechanisms of Heart FailureR01HL129639 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2015 to 2018
$2.6MNovel Mechanisms of LncRNA Mediated Epigenetic Regulation in Cardiac HypertrophyR01HL143058 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2018 to 2021
$2.2MRole of ABCC6 in cardivascular calcificationR01HL137241 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2017 to 2020
$2.1MRole of mesenchymal-endothelial-transition in cardiac hypertrophyR01HL129178 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2015 to 2018
$1.5MNCATS NIH HHS UL1 TR000124NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL114437NHLBI NIH HHS R01 HL129178NHLBI NIH HHS R01 HL129639NHLBI NIH HHS R01 HL137241NHLBI NIH HHS R01 HL143058
Abstract
Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.
Indexed as
Cell LineageOsteogenesisAnimalsBasic Helix-Loop-Helix ProteinsBiomarkersCalcification, PhysiologicCalcinosisCardiomyopathiesCell DifferentiationCell SeparationDiphosphatesDisease Models, AnimalFemaleFibroblastsHumansMaleBasic Helix-Loop-Helix ProteinsBiomarkersDiphosphatesectonucleotide pyrophosphatase phosphodiesterase 1PhosphatesPhosphoric Diester HydrolasesPyrophosphatasesTcf21 protein, mouse
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