title: A single blunt impact on cartilage promotes fibronectin fragmentation and upregulates cartilage degrading stromelysin-1/matrix metalloproteinase-3 in a bovine ex vivo model.
abstract: Post-traumatic osteoarthritis (PTOA) is characterized by progressive cartilage degeneration in injured joints. Since fibronectin-fragments (Fn-fs) degrade cartilage mainly through up-regulating matrix metalloproteinases (MMPs) and pro-inflammatory cytokines, we hypothesized that Fn-fs play a key role in PTOA by promoting chondrolysis in and around injured cartilage. To test this hypothesis, we profiled the catabolic events focusing on fibronectin fragmentation and proteinase expression in bovine osteochondral explants following a single blunt impact on cartilage with a drop tower device which created partial-thickness tissue damage. Injured and control explants were cultured for up to 14 days. The presence of Fn-fs, MMPs (-1, -3, -13), ADAMTS-5 in culture media and in cartilage was determined with immunoblotting. The daily proteoglycan (PG) depletion of cartilage matrix was assessed with DMMB assay. The effect of explant-conditioned media on chondrocytes was also examined with immunoblotting. Impacted cartilage released significantly higher amount of native Fn, three chondrolytic Fn-fs and PG than non-impacted controls did. Those increases coincided with up-regulation of MMP-3 both in culture media and in impacted cartilage. These findings support our hypothesis that PTOA may be propelled by Fn-fs which act as catabolic mediators through up-regulating cartilage-damaging proteinases.
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, 500 Newton Road, 1182 Medical Laboratories, Iowa City, Iowa, 52242.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.forename: Danping
authors.initials: D
authors.lastname: Guo
authors.forename: Gene A
authors.initials: GA
authors.lastname: Homandberg
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Buckwalter
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
mesh_terms: D000818:Animals; D002356:Cartilage / Q000293:injuries* / Q000378:metabolism; D002417:Cattle; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017077:Culture Media, Conditioned; D005353:Fibronectins; D010446:Peptide Fragments; D019278:Matrix Metalloproteinase 3
keywords: cartilage; fibronectin fragments; impact; matrix metalloproteinase-3; proteoglycan