Revisiting the matricellular concept

Matrix Biol. 2014 Jul;37:1-14. doi: 10.1016/j.matbio.2014.07.005. Epub 2014 Jul 24.


The concept of a matricellular protein was first proposed by Paul Bornstein in the mid-1990s to account for the non-lethal phenotypes of mice with inactivated genes encoding thrombospondin-1, tenascin-C, or SPARC. It was also recognized that these extracellular matrix proteins were primarily counter or de-adhesive. This review reappraises the matricellular concept after nearly two decades of continuous investigation. The expanded matricellular family as well as the diverse and often unexpected functions, cellular location, and interacting partners/receptors of matricellular proteins are considered. Development of therapeutic strategies that target matricellular proteins are discussed in the context of pathology and regenerative medicine.

Keywords: CCN; Cell adhesion; Extracellular matrix; Fibulin; Hevin; Matricellular; Osteopontin; Periostin; R-spondin; Regenerative medicine; SPARC; Tenascins; Thrombospondins.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alternative Splicing / physiology*
  • Animals
  • Biomarkers / metabolism*
  • CCN Intercellular Signaling Proteins / metabolism
  • Extracellular Matrix Proteins / metabolism*
  • Extracellular Matrix Proteins / physiology
  • Gene Expression Regulation / physiology*
  • Humans
  • Mice
  • Models, Biological
  • Osteonectin / metabolism
  • Protein Processing, Post-Translational / physiology*
  • Receptors, Antigen / metabolism
  • Thrombospondin 1 / metabolism
  • Tissue Engineering / methods*
  • Translational Medical Research / methods
  • Translational Medical Research / trends*


  • Biomarkers
  • CCN Intercellular Signaling Proteins
  • Extracellular Matrix Proteins
  • Osteonectin
  • Receptors, Antigen
  • Thrombospondin 1
  • Tn receptor