ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Osteopontin stimulates apoptosis in adult cardiac myocytes via the involvement of CD44 receptors, mitochondrial death pathway, and endoplasmic reticulum stress.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 70 citations in OpenAlex.
- Role of osteopontin in cancer: From pathogenesis to therapeutics (Review).Oncology reports · 2025Review
- Epicardial Adipose Tissue-A Novel Therapeutic Target in Obesity Cardiomyopathy.International journal of molecular sciences · 2025Review
- Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies.Biology · 2025Review
- Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.International journal of molecular sciences · 2024Article
- Potential mechanism of TMEM2/CD44 in endoplasmic reticulum stress‑induced neuronal apoptosis in a rat model of traumatic brain injury.International journal of molecular medicine · 2023Article
- CD44 regulates Epac1-mediated β-adrenergic-receptor-induced CaJournal of biomedical science · 2023Article
- Integrative multiomic analyses of dorsal root ganglia in diabetic neuropathic pain using proteomics, phospho-proteomics, and metabolomics.Scientific reports · 2022Article
- Clinical and Molecular Implications of Osteopontin in Heart Failure.Current issues in molecular biology · 2022Review
- Mitochondria-Targeted Drug Delivery in Cardiovascular Disease: A Long Road to Nano-Cardio Medicine.Pharmaceutics · 2020Review
- Exogenous ubiquitin attenuates hypoxia/reoxygenation-induced cardiac myocyte apoptosis via the involvement of CXCR4 and modulation of mitochondrial homeostasis.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2020Article
- Mix and (mis-)match - The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart.Biochimica et biophysica acta. Molecular cell research · 2020Review
- The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis.Journal of orthopaedic surgery and research · 2019Article
- Elevated CD44 expression predicts poor prognosis in patients with low-grade glioma.Oncology letters · 2019Article
- The Extracellular Matrix in Ischemic and Nonischemic Heart Failure.Circulation research · 2019Review
- Single-cell RNA sequencing reveals novel gene expression signatures of trastuzumab treatment in HER2+ breast cancer: A pilot study.Medicine · 2019Article
- Osteopontin b and c Splice isoforms in Leukemias and Solid Tumors: Angiogenesis Alongside ChemoresistanceAsian Pacific journal of cancer prevention : APJCP · 2018Review
- The interaction between mitochondria and oncoviruses.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- NF2 signaling pathway plays a pro-apoptotic role in β-adrenergic receptor stimulated cardiac myocyte apoptosis.PloS one · 2018Article
- Preparation of A Spaceflight: Apoptosis Search in Sutured Wound Healing Models.International journal of molecular sciences · 2017Article
- Spatiotemporal expression of osteopontin in the striatum of rats subjected to the mitochondrial toxin 3-nitropropionic acid correlates with microcalcification.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased osteopontin (OPN) expression associates with increased myocyte apoptosis and myocardial dysfunction. The objective of this study was to identify the receptor for OPN and get insight into the mechanism by which OPN induces cardiac myocyte apoptosis. Adult rat ventricular myocytes (ARVMs) and transgenic mice expressing OPN in a myocyte-specific manner were used for in vitro and in vivo studies. Treatment with purified OPN (20 nM) protein or adenoviral-mediated OPN expression induced apoptosis in ARVMs. OPN co-immunoprecipitated with CD44 receptors, not with β1 or β3 integrins. Proximity ligation assay confirmed interaction of OPN with CD44 receptors. Neutralizing anti-CD44 antibodies inhibited OPN-stimulated apoptosis. OPN activated JNKs and increased expression of Bax and levels of cytosolic cytochrome c, suggesting involvement of mitochondrial death pathway. OPN increased endoplasmic reticulum (ER) stress, as evidenced by increased expression of Gadd153 and activation of caspase-12. Inhibition of JNKs using SP600125 or ER stress using salubrinal or caspase-12 inhibitor significantly reduced OPN-stimulated apoptosis. Expression of OPN in adult mouse heart in myocyte-specific manner associated with decreased left ventricular function and increased myocyte apoptosis. In the heart, OPN expression increased JNKs and caspase-12 activities, and expression of Bax and Gadd153. Thus, OPN, acting via CD44 receptors, induces apoptosis in myocytes via the involvement of mitochondrial death pathway and ER stress.
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