title: Matrilin-4 is processed by ADAMTS-5 in late Golgi vesicles present in growth plate chondrocytes of defined differentiation state.
abstract: The two aggrecanases ADAMTS-4 and ADAMTS-5 have been shown to not only play roles in the breakdown of cartilage extracellular matrix in osteoarthritis, but also mediate processing of matrilins in the secretory pathway. The matrilins are adaptor proteins with a function in connecting fibrillar and network-like components in the cartilage extracellular matrix. Cleavage resulting in processed matrilins with fewer ligand-binding subunits could make these less efficient in providing matrix cohesion. In this study, the processing and degradation of matrilin-4 during cartilage remodeling in the growth plate of the developing mouse long bones were studied in greater detail. We show that ADAMTS-5 and a matrilin-4 neoepitope, revealed upon ADAMTS cleavage, colocalize in prehypertrophic/hypertrophic chondrocytes while they are not detected in proliferating chondrocytes of the growth plate. ADAMTS-5 and the cleaved matrilin-4 are preferentially detected in vesicles derived from the Golgi apparatus. The matrilin-4 neoepitope was not observed in the growth plate of ADAMTS-5 deficient mice. We propose that in the growth plate ADAMTS-5, and not ADAMTS-4, has a physiological function in the intracellular processing of matrilins and potentially of other extracellular matrix proteins.
authors.affiliation: Center for Biochemistry, University of Cologne, Germany.
authors.forename: Gergely
authors.initials: G
authors.lastname: Groma
authors.forename: Ivan
authors.initials: I
authors.lastname: Grskovic
authors.forename: Sylvia
authors.initials: S
authors.lastname: Schael
authors.forename: Harald W A
authors.initials: HW
authors.lastname: Ehlen
authors.forename: Raimund
authors.initials: R
authors.lastname: Wagener
authors.forename: Amanda
authors.initials: A
authors.lastname: Fosang
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.forename: Bent
authors.initials: B
authors.lastname: Brachvogel
authors.forename: Frank
authors.initials: F
authors.lastname: Zaucke
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology* / Q000378:metabolism; D006614:Hindlimb / Q000166:cytology / Q000378:metabolism; D064235:Matrilin Proteins; D051379:Mice; D018345:Mice, Knockout; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; C577547:Matn4 protein, mouse; D064235:Matrilin Proteins; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse