Journal article
A SINGLE BLUNT IMPACT ON CARTILAGE PROMOTES FIBRONECTIN FRAGMENTATION AND UPREGULATES CARTILAGE DEGRADING STROMELYSIN-1/MATRIX METALLOPROTEINASE-3 IN A BOVINE EX-VIVO MODEL
Journal of orthopaedic research, Vol.32(6), pp.811-818
06/2014
DOI: 10.1002/jor.22610
PMCID: PMC4034576
PMID: 24610678
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 conditioned 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.
Details
- Title: Subtitle
- A SINGLE BLUNT IMPACT ON CARTILAGE PROMOTES FIBRONECTIN FRAGMENTATION AND UPREGULATES CARTILAGE DEGRADING STROMELYSIN-1/MATRIX METALLOPROTEINASE-3 IN A BOVINE EX-VIVO MODEL
- Creators
- Lei Ding - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USADanping Guo - Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USAGene A Homandberg - Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USAJoseph A Buckwalter - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USAJames A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.32(6), pp.811-818
- DOI
- 10.1002/jor.22610
- PMID
- 24610678
- PMCID
- PMC4034576
- NLM abbreviation
- J Orthop Res
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Grant note
- name: US DHHS, National Institutes of Health/NIAMS, award: P50 AR055533; name: Merit Review Award from the Department of Veterans Affairs
- Language
- English
- Date published
- 06/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040289602771
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