title: Cartilage oligomeric matrix protein promotes cell attachment via two independent mechanisms involving CD47 and alphaVbeta3 integrin.
abstract: Cartilage oligomeric matrix protein (COMP) is a pentameric approximately 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 alphaVbeta3 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 alphaVbeta3 integrin and that a consequence of cell attachment to COMP is the specific induction of fascin-stabilized actin microspikes.
authors.affiliation: Medical Genetics Institute, Steven Spielberg Pediatric Research Center, Los Angeles, CA 90048, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rock
authors.forename: Paul
authors.initials: P
authors.lastname: Holden
authors.forename: William A
authors.initials: WA
authors.lastname: Horton
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Cohn
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein; D002448:Cell Adhesion / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008022:Ligaments / Q000166:cytology / Q000378:metabolism; D064235:Matrilin Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D051928:CD47 Antigen; D002352:Carrier Proteins; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D039302:Integrin alphaVbeta3; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D008840:Microfilament Proteins; D010455:Peptides; C577553:TSP5 protein, human; C020324:fascin