Differential regulation of gelatinases by transforming growth factor beta-1 in normal equine chondrocytes.
Abstract: Cartilage destruction in osteoarthritis (OA) is associated with increased levels of several matrix metalloproteinases (MMPs), including the gelatinases MMP-2 and MMP-9. While increases in some MMPs may be destructive, up-regulation of others may result from increases in normal tissue turnover. The production of MMP-2 and MMP-9 by the anabolic transforming growth factor beta-1 (TGF-beta1) in normal equine chondrocytes was investigated. Methods: Equine chondrocytes from clinically normal femoropatellar joints were maintained in alginate beads. After serum deprivation, cells were exposed to TGF-beta1 at several concentrations for varying times. Activities of MMP-2 and MMP-9 were estimated by gelatin zymography, while mRNA for MMP-2, MMP-9 and collagen type II were detected using reverse transcription-polymerase chain reaction. Results: Stimulation with TGF-beta1 differentially regulated MMP-2 and MMP-9, with strong up-regulation of both MMP-9 mRNA and enzyme. Increases in MMP-9 enzyme were dose-dependent (0-49 h). There is some evidence suggesting a slight reduction in MMP-2 release following stimulation. Collagen type II mRNA was transiently increased following stimulation. Conclusions: The different effects of TGF-beta1 on MMP-2 and MMP-9 production by normal chondrocytes suggests different roles for these enzymes. The increases in both MMP-9 and collagen type II mRNA following stimulation may suggest a role for MMP-9 in tissue maintenance. Therefore, increased MMP-9 may be secondary to, as distinct from a cause of, cartilage damage.
Copyright 2001 OsteoArthritis Research Society International.
Publication Date: 2001-06-12 PubMed ID: 11399096DOI: 10.1053/joca.2000.0392Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explored how transforming growth factor beta-1 (TGF-beta1) affects the production of gelatinases MMP-2 and MMP-9 in healthy equine chondrocytes. It highlighted differential regulation of MMP-2 and MMP-9, potentially influencing cartilage degradation in osteoarthritis.
Methods
- The study used chondrocytes extracted from normal femoropatellar joints of horses.
- These cells were kept in alginate beads and starved of serum prior to the experiment.
- The researchers exposed the cells to various concentrations of TGF-beta1 over different time periods.
- They estimated the activities of MMP-2 and MMP-9 using a method called gelatin zymography.
- mRNA related to MMP-2, MMP-9, and collagen type II was then detected using reverse transcription-polymerase chain reaction.
Findings
- The exposure of chondrocytes to TGF-beta1 resulted in differential regulation of MMP-2 and MMP-9.
- There was a significant increase in both the mRNA and enzyme of MMP-9. This increase was dose-dependent: the higher the TGF-beta1 dose, the greater the increase in MMP-9 production. This effect was monitored over a period of 0 to 49 hours.
- There was only weak evidence suggesting a slight decrease in MMP-2 after exposure to TGF-beta1.
- mRNA for collagen type II briefly increased after stimulation.
Conclusions
- The divergent effects of TGF-beta1 on the production of MMP-2 and MMP-9 imply different roles for these enzymes in cartilage metabolism.
- The increase in MMP-9 and collagen type II mRNA suggests a possible role for MMP-9 in the maintenance of cartilage tissue.
- The research proposes that an increase in MMP-9 might not be a cause but a secondary result of cartilage degradation. Therefore, it may reflect efforts of tissue repair rather than contribute to the damage.
Cite This Article
APA
Thompson CC, Clegg PD, Carter SD.
(2001).
Differential regulation of gelatinases by transforming growth factor beta-1 in normal equine chondrocytes.
Osteoarthritis Cartilage, 9(4), 325-331.
https://doi.org/10.1053/joca.2000.0392 Publication
Researcher Affiliations
- Connective Tissue Research Group, Faculty of Veterinary Science, University of Liverpool, Liverpool, L69 3BX, UK.
MeSH Terms
- Animals
- Cartilage / metabolism
- Chondrocytes / physiology
- Collagen / metabolism
- Hindlimb
- Horses
- Joints
- Matrix Metalloproteinase 2 / biosynthesis
- Matrix Metalloproteinase 9 / biosynthesis
- RNA, Messenger / metabolism
- Transforming Growth Factor beta / pharmacology
Citations
This article has been cited 2 times.- Ongchai S, Somnoo O, Kongdang P, Peansukmanee S, Tangyuenyong S. TGF-β1 upregulates the expression of hyaluronan synthase 2 and hyaluronan synthesis in culture models of equine articular chondrocytes.. J Vet Sci 2018 Nov 30;19(6):735-743.
- Baugé C, Girard N, Lhuissier E, Bazille C, Boumediene K. Regulation and Role of TGFβ Signaling Pathway in Aging and Osteoarthritis Joints.. Aging Dis 2014 Dec;5(6):394-405.
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