Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage.
Abstract: The concentration-effect relationships of phenylbutazone, indomethacin, betamethasone, pentosan polysulphate (PPS) and polysulphated glycosaminoglycan (PSGAG), on proteoglycan synthesis by equine cultured chondrocytes grown in monolayers, and articular cartilage explants were measured. The effect of PSGAG on interleukin-1beta induced suppression of proteogycan synthesis was also investigated. Proteoglycan synthesis was measured by scintillation assay of radiolabelled sulphate (35SO4) incorporation. Polysulphated glycosaminoglycan and PPS stimulated proteoglycan synthesis in chondrocyte monolayers in a concentration-related manner with maximal effects being achieved at a concentration of 10 microg/mL. Polysulphated glycosaminoglycan reversed the concentration-related suppression of proteoglycan synthesis induced by interleukin-1beta. Neither PSGAG nor PPS exerted significant effects on radiolabel incorporation in cartilage explants. Betamethasone suppressed proteoglycan synthesis by both chondrocytes and explants at high concentrations (0.1-100 microg/mL), but the effect was not concentration-related. At low concentrations (0.001-0.05 microg/mL) betamethasone neither increased nor decreased proteoglycan synthesis. Phenylbutazone and indomethacin increased radiolabel incorporation in chondrocyte cultures but not in cartilage explants at low (0.1, 1 and 10 microg/mL), but not at high (20 and 100 microg/mL) concentrations. These findings may be relevant to the clinical use of these drugs in the treatment of equine disease.
Publication Date: 2002-09-06 PubMed ID: 12213118DOI: 10.1046/j.1365-2885.2002.00404.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper studies how different anti-arthritic drugs impact the production of proteoglycans – crucial components for cartilage health – in horse cartilage cells and tissues, which can have implications for the treatment of equine arthritis.
Anti-arthritic Drugs and Proteoglycan Synthesis
- The researchers first explained that they examined how various anti-arthritic drugs — phenylbutazone, indomethacin, betamethasone, pentosan polysulphate (PPS), and polysulphated glycosaminoglycan (PSGAG) — affect the production of proteoglycans in equine cultured chondrocytes (cartilage cells grown in a lab setting).
- They determined proteoglycan synthesis by measuring the incorporation of a radioactive form of sulphate (35SO4) into the proteoglycan molecule. The more sulphate incorporated, the more proteoglycan being produced.
Impact of Each Drug
- They found that PSGAG and PPS stimulated the synthesis of proteoglycans in a concentration-dependent manner, reaching peak effectiveness at a concentration of 10 micrograms per millilitre. PSGAG also countered the effects of a substance called interleukin-1beta which suppresses proteoglycan synthesis.
- However, these effects of PSGAG and PPS were not observed in cartilage tissue samples (explants).
- Betamethasone suppressed proteoglycan synthesis at high concentrations, but showed no effect at low concentrations.
- Phenylbutazone and indomethacin increased proteoglycan synthesis only at low concentrations and only in isolated chondrocyte cultures, not in cartilage tissue samples.
Clinical Implications
- The study concluded that these results could be important in the clinical use of these drugs for treating equine diseases like arthritis.
- Understanding how these drugs impact equine cartilage on a molecular level can help in developing effective treatment strategies.
Cite This Article
APA
Frean SP, Cambridge H, Lees P.
(2002).
Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage.
J Vet Pharmacol Ther, 25(4), 289-298.
https://doi.org/10.1046/j.1365-2885.2002.00404.x Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, Hawkshead Campus, North Mymms, Herts AL9 7TA, UK. sfrean@rvc.ac.uk
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Cells, Cultured
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Dose-Response Relationship, Drug
- Horses
- Proteoglycans / biosynthesis
Citations
This article has been cited 3 times.- Vázquez-Meza H, de Piña MZ, Pardo JP, Riveros-Rosas H, Villalobos-Molina R, Piña E. Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis.. BMC Biochem 2013 May 30;14:13.
- Farkas B, Kvell K, Czömpöly T, Illés T, Bárdos T. Increased chondrocyte death after steroid and local anesthetic combination.. Clin Orthop Relat Res 2010 Nov;468(11):3112-20.
- Lees P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice.. Inflammopharmacology 2003;11(4):385-99.
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