Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling

Cell Stem Cell. 2011 Nov 4;9(5):420-32. doi: 10.1016/j.stem.2011.08.013.


Cardiomyocyte remodeling, which includes partial dedifferentiation of cardiomyocytes, is a process that occurs during both acute and chronic disease processes. Here, we demonstrate that oncostatin M (OSM) is a major mediator of cardiomyocyte dedifferentiation and remodeling during acute myocardial infarction (MI) and in chronic dilated cardiomyopathy (DCM). Patients suffering from DCM show a strong and lasting increase of OSM expression and signaling. OSM treatment induces dedifferentiation of cardiomyocytes and upregulation of stem cell markers and improves cardiac function after MI. Conversely, inhibition of OSM signaling suppresses cardiomyocyte remodeling after MI and in a mouse model of DCM, resulting in deterioration of heart function after MI but improvement of cardiac performance in DCM. We postulate that dedifferentiation of cardiomyocytes initially protects stressed hearts but fails to support cardiac structure and function upon continued activation. Manipulation of OSM signaling provides a means to control the differentiation state of cardiomyocytes and cellular plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiotonic Agents / metabolism
  • Cell Cycle / drug effects
  • Cell Dedifferentiation* / drug effects
  • DNA / biosynthesis
  • Fluorescent Antibody Technique
  • Gene Deletion
  • Gene Expression Regulation / drug effects
  • Heart Function Tests / drug effects
  • Humans
  • Mice
  • Mice, Transgenic
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology*
  • Oncostatin M / metabolism*
  • Oncostatin M / pharmacology
  • Oncostatin M Receptor beta Subunit / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / physiology*


  • Biomarkers
  • Cardiotonic Agents
  • Oncostatin M Receptor beta Subunit
  • Oncostatin M
  • DNA