In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen.
Abstract: The effects of hyaluronan and carprofen (both racemic mixture and separate R and S enantiomers) on proteoglycan (PG) synthesis by equine cultured chondrocytes and cartilage explants were examined. Hyaluronan stimulated PG synthesis in both cell and explant cultures. The concentration-response curve of the latter was bell-shaped. Racemic carprofen and R and S enantiomers also stimulated PG synthesis, although concentration-response relationships varied for each preparation and high concentrations inhibited synthesis. It was concluded that (a) hyaluronan exerts a stimulatory effect on PG synthesis at low concentrations and (b) stimulatory effects of carprofen on PG synthesis are, to some degree, enantioselective with the carprofen S-enantiomer exerting the greatest effect. Hyaluronan and carprofen are used clinically despite incompletely understood mechanisms of action. These results suggest (a) hyaluronan and carprofen might exert an anti-arthritic action through stimulation of PG synthesis and (b) there is possible justification for therapeutic administration of enantiomeric rather than racemic carprofen.
Copyright 1999 Harcourt Publishers Ltd.
Publication Date: 1999-09-30 PubMed ID: 10502490DOI: 10.1053/rvsc.1999.0328Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study explores the impact of hyaluronan and carprofen on the synthesis of proteoglycan by horse chondrocytes and cartilage explants in culture. Findings suggest that both of these substances may prompt an anti-arthritic action through stimulating proteoglycan synthesis.
Hyaluronan and Proteoglycan Synthesis
- The study found that hyaluronan was able to stimulate the synthesis of proteoglycan (PG), an essential component for the elasticity and resiliency of cartilage. This was observed in both equine chondrocyte cultures (cartilage cells) and cartilage explants (tissue samples).
- The effects of hyaluronan on proteoglycan synthesis followed a bell-shaped concentration-response curve. This suggests that the stimulation of PG synthesis is greatest at a certain concentration of hyaluronan, with the effect diminishing at both lower and higher concentrations.
Carprofen and Proteoglycan Synthesis
- Similar to hyaluronan, it was found that carprofen, in its racemic form and as separate R and S enantiomers, also stimulated proteoglycan synthesis. An enantiomer refers to one of two stereoisomers that are mirror images of each other.
- The effects of carprofen on proteoglycan synthesis were found to be enantioselective to some degree, with the S-enantiomer of carprofen having the greatest effect. Enantioselectivity is the preference of a certain enantiomer over its mirror image.
- However, unlike hyaluronan, high concentrations of carprofen were found to inhibit proteoglycan synthesis. The concentration effect varied with each preparation of carprofen.
Therapeutic Implications and Conclusion
- This study suggests that hyaluronan and carprofen could potentially exhibit anti-arthritic effects. This is likely due to their ability to stimulate the synthesis of proteoglycans, which aid in the elasticity and resistance of cartilage, crucial characteristics that counteract arthritis effects.
- The study also suggests a potential justification for therapeutically administering the S-enantiomer, rather than the racemic form of carprofen, due to its greater effect on proteoglycan synthesis.
- However, despite their clinical use, the researchers note that the mechanisms of action of hyaluronan and carprofen are not entirely understood, making further research necessary.
Cite This Article
APA
Frean SP, Abraham LA, Lees P.
(1999).
In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen.
Res Vet Sci, 67(2), 183-190.
https://doi.org/10.1053/rvsc.1999.0328 Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts, AL9 7TA, UK. sfrean@rvc.ac.uk
MeSH Terms
- Adjuvants, Immunologic / pharmacology
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Carbazoles / pharmacology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Cells, Cultured
- Horses
- Hyaluronic Acid / pharmacology
- Proteoglycans / biosynthesis
Citations
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