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Molecular and Cellular Biochemistry

, Volume 338, Issue 1–2, pp 215–224 | Cite as

Cartilage oligomeric matrix protein promotes cell attachment via two independent mechanisms involving CD47 and αVβ3 integrin

  • Matthew J. Rock
  • Paul Holden
  • William A. Horton
  • Daniel H. Cohn
Article

Abstract

Cartilage oligomeric matrix protein (COMP) is a pentameric ~524 kDa multidomain extracellular matrix protein and is the fifth member of the thrombospondin family. COMP is abundantly expressed in proliferating and hypertrophic chondrocytes of the growth plate, articular cartilage, synovium, tendon, and ligament. The spatial localization of COMP highlights its importance in the phenotypes of pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), COMP disorders that are characterized by disproportionate short stature, brachydactyly, scoliosis, early-onset osteoarthritis, and joint hypermobility. In this study, the role of COMP in ligament was investigated with a series of cell attachment assays using ligament cells binding to COMP. A dose-dependent cell attachment activity was found, which was inhibited by a peptide containing the SFYVVMWK amino acid sequence derived from the globular C-terminal domain of COMP. This activity was independent of the recently described RGD-dependent attachment activity. Function-blocking antibodies to CD47 and αVβ3 integrin reduced cell attachment to COMP, implicating the participation of these cell surface molecules in COMP cell binding. Immunofluorescence studies showed that cell attachment to COMP induced the formation of lamellae containing F-actin microspikes associated with fascin. We propose that COMP promotes cell attachment via two independent mechanisms involving cell surface CD47 and αVβ3 integrin and that a consequence of cell attachment to COMP is the specific induction of fascin-stabilized actin microspikes.

Keywords

COMP Extracellular matrix Cell adhesion Signaling Actin cytoskeleton 

Notes

Acknowledgments

This study was supported in part by grants from the National Institutes of Health (AR493139 and HD22657 (DHC) and the Shriners Hospitals for Children (WAH). Daniel Cohn is a Winnick Family Clinical Research Scholar supported by the General Clinical Research Center at Cedars-Sinai under NCRR grant M01-RR00425. Paul Holden was a recipient of a Shriners Research Fellowship Award. We thank Deborah Krakow for assistance with obtaining cartilage samples, Vincent Funari for help with statistical analysis, Vladimir Vilim for COMP monoclonal antibodies, and MaryAnn Weiss and David Eyre for analyzing COMP purity by mass spectrometry.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Matthew J. Rock
    • 1
  • Paul Holden
    • 2
    • 3
  • William A. Horton
    • 2
    • 3
  • Daniel H. Cohn
    • 1
    • 4
    • 5
  1. 1.Medical Genetics InstituteSteven Spielberg Pediatric Research CenterLos AngelesUSA
  2. 2.Research CenterShriners Hospitals for ChildrenPortlandUSA
  3. 3.Department of Molecular and Medical GeneticsOregon Health & Science UniversityPortlandUSA
  4. 4.Department of Human GeneticsDavid Geffen School of Medicine at UCLALos AngelesUSA
  5. 5.Department of PediatricsDavid Geffen School of Medicine at UCLALos AngelesUSA

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