Fibronectin fragments cause release and degradation of collagen-binding molecules from equine explant cultures.
Abstract: Previous experiments have shown that addition of fragmented fibronectin can induce cartilage chondrolysis. In this study we investigated the fate of the collagen- and cell-binding molecules Cartilage oligomeric matrix protein (COMP) and chondroadherin. Methods: Equine articular cartilage explants were stimulated with the C-terminal and the N-terminal heparin-binding fragments of fibronectin respectively, and the conditioned media were analysed by both quantitative (ELISA) and qualitative (mass spectrometry, Western blots) methods. Results: Both COMP and chondroadherin were released in a dose-dependent manner upon stimulation with the Hep II (C-terminal heparin-binding) fragment of fibronectin. The kinetics of release for the two components differed. Moreover, COMP was degraded while no fragments of chondroadherin could be detected. Stimulation with Hep II also induced production of nitric oxide in a dose-dependent manner. We compared effects of the Hep II fragment with that of Hep I (the N-terminal heparin-binding fragment of fibronectin) and found that while Hep I did indeed elicit release of COMP and chondroadherin, the response was less potent, and production of nitric oxide was negligible. The responses to both fragments were elicited within 24h. Conclusions: We suggest that the events described here may be early, critical stages in cartilage destruction preceding collagen destruction.
Publication Date: 2004-01-16 PubMed ID: 14723874DOI: 10.1016/j.joca.2003.10.008Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates a possible early indication of cartilage destruction via the release and degradation of collagen-binding molecules (COMP and chondroadherin) when exposed to fibronectin fragments in horse cartilage.
Investigation Method
- The team used fragments from the C-terminal (Hep II) and the N-terminal (Hep I) heparin-binding parts of fibronectin to stimulate equine articular cartilage explants.
- The conditioned media post-stimulation were analyzed using quantitative (ELISA) and qualitative (mass spectrometry, Western blots) methods to check for the release of the collagen- and cell-binding molecules COMP and chondroadherin.
Study Findings
- Both COMP and chondroadherin were released in larger amounts with increasing dose of Hep II stimulation. The rate of release for COMP and chondroadherin differed from each other.
- COMP was found to be degraded while no fragments of chondroadherin could be detected, implying that chondroadherin remains intact.
- Stimulation of cartilage explants with Hep II also led to an increased production of nitric oxide, a chemical typically related to inflammation and immune response, in a dose-dependent manner.
- Comparison of effects induced by Hep II and Hep I fragments of fibronectin showed a lesser response to Hep I- both in terms of COMP and chondroadherin release, and negligible production of nitric oxide.
- The effect of fibronectin fragments on the equine cartilage explants, in terms of COMP and chondroadherin release, was noticeable within 24 hours.
Conclusions
- Based on these results, the researchers propose that these observed alterations may represent the early and pivotal stages in cartilage destruction that occur even before collagen begins to breakdown.
Cite This Article
APA
Johnson A, Smith R, Saxne T, Hickery M, Heinegård D.
(2004).
Fibronectin fragments cause release and degradation of collagen-binding molecules from equine explant cultures.
Osteoarthritis Cartilage, 12(2), 149-159.
https://doi.org/10.1016/j.joca.2003.10.008 Publication
Researcher Affiliations
- Department of Cell and Molecular Biology, Section for Connective Tissue Biology, Lund University, Lund, Sweden.
MeSH Terms
- Animals
- Azides / pharmacology
- Blotting, Western / methods
- Cartilage, Articular / drug effects
- Cartilage, Articular / physiology
- Chondrocytes / physiology
- Collagen / metabolism
- Culture Media
- Culture Techniques
- Cyclopentanes / pharmacology
- Electrophoresis, Polyacrylamide Gel / methods
- Enzyme-Linked Immunosorbent Assay / methods
- Extracellular Matrix Proteins / analysis
- Extracellular Matrix Proteins / physiology
- Fibronectins / physiology
- Forelimb
- Glycoproteins / analysis
- Glycoproteins / physiology
- Horses
- Mass Spectrometry / methods
- Matrilin Proteins
- Protein Denaturation
Citations
This article has been cited 10 times.- Smith R, Önnerfjord P, Holmgren K, di Grado S, Dudhia J. Development of a Cartilage Oligomeric Matrix Protein Neo-Epitope Assay for the Detection of Intra-Thecal Tendon Disease. Int J Mol Sci 2020 Mar 20;21(6).
- Apte SS. Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J 2016 Jan 1;473(1):e1-4.
- Przybysz M, Borysewicz K, Kątnik-Prastowska I. Fibronectin molecular status determination useful to differentiate between rheumatoid arthritis and systemic lupus erythematosus patients. Rheumatol Int 2013 Jan;33(1):37-43.
- Sofat N, Robertson SD, Wait R. Fibronectin III 13-14 domains induce joint damage via Toll-like receptor 4 activation and synergize with interleukin-1 and tumour necrosis factor. J Innate Immun 2012;4(1):69-79.
- Shohani B, Orazizadeh M, Hashemitabar M, Heinegard D. Degradation of extracellular matrix molecules in interleukin-1α treated bovine nasal cartilage. Iran Biomed J 2010 Oct;14(4):158-63.
- Sofat N. Analysing the role of endogenous matrix molecules in the development of osteoarthritis. Int J Exp Pathol 2009 Oct;90(5):463-79.
- Tseng S, Reddi AH, Di Cesare PE. Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis. Biomark Insights 2009 Feb 17;4:33-44.
- Smith MM, Melrose J. COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair. Int J Mol Sci 2025 Sep 19;26(18).
- Gagliardi R, Koch DW, Loeser R, Schnabel LV. Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype. J Orthop Res 2025 Feb;43(2):292-303.
- Hutcherson CW, Mao M, Thakur B, Dhaher YY. Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading. Cartilage 2024 Dec;15(4):417-427.
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