IL-1 beta induces the degradation of equine articular cartilage by a mechanism that is not mediated by nitric oxide.
Abstract: Proteoglycan degradation was induced in young equine articular cartilage explants cultured for eight days in the presence of 50 ng/ml recombinant human interleukin-1 beta. Degradation was initiated after 6 hours of exposure to the cytokine. This was accompanied by an induction of nitric oxide synthesis and a decrease in the incorporation of [36S]sulphate into the glycosaminoglycan chains of proteoglycans. The addition of 1mM N-iminoethyl-L-ornithine (an inhibitor of nitric oxide synthase) to the explant cultures in the presence of rhIL-1 beta suppressed the synthesis of NO and restored proteoglycan synthesis to control levels. However, treatment of explants with LNIO did not overcome proteoglycan degradation. These results indicate that although IL1 beta regulates both proteoglycan synthesis and degradation in equine cartilage explants, only the inhibition of proteoglycan synthesis is mediated by nitric oxide.
Publication Date: 1997-09-23 PubMed ID: 9299456DOI: 10.1006/bbrc.1997.7246Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates how the protein IL-1 beta contributes to the breakdown of equine (horse) joint cartilage, discovering that nitric oxide seems to mediate only the inhibition of proteoglycan synthesis, not the overall degradation of the cartilage.
Objective and Methods
- The study examined the effect of the protein interleukin-1 beta (IL-1 beta) on proteoglycan degradation in equine articular (joint) cartilage.
- Articular cartilage explants, derived from young horses, were cultured for eight days in the presence of a recombinant human version of IL-1 beta (rhIL-1 beta).
- Proteoglycan degradation was noticed in the explants after 6 hours of cytokine exposure. This process was accompanied by increased synthesis of nitric oxide and decreased incorporation of sulphate into the glycosaminoglycan chains of proteoglycans.
- The researchers tested the role of nitric oxide in the degradation process by adding a specific inhibitor (N-iminoethyl-L-ornithine or LNIO) to the cultures together with IL-1 beta. This addition suppressed nitric oxide synthesis and restored proteoglycan synthesis back to normal levels.
Findings and Conclusion
- The inhibition of nitric oxide alone did not prevent proteoglycan degradation, though it did restore proteoglycan synthesis to normal levels.
- This suggests that while IL-1 beta influences both proteoglycan synthesis and degradation, only the inhibition of proteoglycan synthesis is affected by nitric oxide.
- Therefore, the study concludes that the IL-1 beta induced degradation of equine articular cartilage is by a mechanism that’s not mediated by nitric oxide.
Implications
- The results provide new insights into the complex biological signaling that leads to joint cartilage breakdown. This knowledge may be critical for developing more effective treatments to slow down or prevent joint diseases such as arthritis in horses and potentially in humans too.
- Given that nitric oxide only seems to affect the inhibition of proteoglycan synthesis and not degradation, other mechanisms must play a role in the degradation process, warranting further research.
Cite This Article
APA
Bird JL, Wells T, Platt D, Bayliss MT.
(1997).
IL-1 beta induces the degradation of equine articular cartilage by a mechanism that is not mediated by nitric oxide.
Biochem Biophys Res Commun, 238(1), 81-85.
https://doi.org/10.1006/bbrc.1997.7246 Publication
Researcher Affiliations
- Department of Farm Animal and Equine Medicine and Surgery, Royal Veterinary College, Hatfield, Hertsfordshire, United Kingdom.
MeSH Terms
- Animals
- Carpus, Animal
- Cartilage, Articular / cytology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Culture Media / metabolism
- Electrophoresis, Agar Gel
- Electrophoresis, Polyacrylamide Gel
- Horses
- Humans
- Interleukin-1 / pharmacology
- Nitric Oxide / physiology
- Organ Culture Techniques
- Proteoglycans / antagonists & inhibitors
- Proteoglycans / biosynthesis
- Proteoglycans / isolation & purification
- Recombinant Proteins / pharmacology
- Time Factors
Citations
This article has been cited 5 times.- Houtman E, van Hoolwerff M, Lakenberg N, Suchiman EHD, van der Linden-van der Zwaag E, Nelissen RGHH, Ramos YFM, Meulenbelt I. Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis. Rheumatol Ther 2021 Mar;8(1):499-515.
- Marques-Smith P, Kallerud AS, Johansen GM, Boysen P, Jacobsen AM, Reitan KM, Henriksen MM, Löfgren M, Fjordbakk CT. Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?. BMC Vet Res 2020 Jun 8;16(1):181.
- Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?. Front Vet Sci 2018;5:208.
- Stevens AL, Wheeler CA, Tannenbaum SR, Grodzinsky AJ. Nitric oxide enhances aggrecan degradation by aggrecanase in response to TNF-alpha but not IL-1beta treatment at a post-transcriptional level in bovine cartilage explants. Osteoarthritis Cartilage 2008 Apr;16(4):489-97.
- Usimaki A, Ciamillo SA, Barot D, Linardi RL, Engiles JB, Ortved KF. Single injection of intra-articular autologous protein solution in horses with acute interleukin-1B-induced synovitis decreases joint pathology scores. Equine Vet J 2025 May;57(3):806-816.
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