Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation

摘要: Mutations in human cartilage oligomeric matrix protein (COMP) have been linked to the development of pseudoachondroplasia and multiple epiphyseal dysplasia; however, functions both wild-type mutant COMP skeletogenesis remain unknown. In an effort define biological COMP, a functional genetic screen based on yeast two-hybrid system was performed. This led identification granulin-epithelin precursor (GEP), autocrine growth factor, as COMP-associated partner. directly binds GEP vitro vivo, revealed by pull down co-immunoprecipitation assays. selectively interacts with epidermal factor repeat domain but not other three domains COMP. The granulin A unit is required sufficient for association co-localizes predominantly pericellular transfected rat chondrosarcoma cell primary chondrocytes. Staining musculoskeletal tissues day 19 mouse embryo antibodies restricted chondrocytes lower proliferative upper hypertrophic zones. Overexpression stimulates proliferation chondrocytes, this stimulation enhanced addition, appears be GEP-mediated chondrocyte proliferation, since induced dramatically inhibited anti-COMP antibody. These findings provide first evidence linking identifying previously unrecognized (i.e. GEP) cartilage.