Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac.
Abstract: The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) -2, -8 and -9 in horses. To evaluate MMP-2 and -9 activities and the effect of non-steroidal anti-inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra-articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra-articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP-2 and MMP-9 activity by gelatin zymography or for MMP-8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP-8 and activity of both the latent and the active forms of MMP-2 and -9, among which the active form of MMP-2 increased the most. MMP-9 levels declined to pre-induction levels within 2 weeks, whereas levels of MMP-2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP-9 activity and especially levels of active forms of MMP-2 activity may be valuable to predict the time of occurrence of arthritis in horses.
Publication Date: 2006-08-12 PubMed ID: 16901276DOI: 10.1111/j.1439-0442.2006.00837.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research focuses on analyzing the effects of artificially induced arthritis on horses, particularly on changes in protein enzymes known as Matrix Metalloproteinases (MMP-2, -8, -9). The study also investigates the effectiveness of a non-steroidal anti-inflammatory drug, bufexamac, in treating the condition.
Study Overview
- The study induced aseptic arthritis in 24 standardbred horses with the use of amphotericin B via intra-articular injection in the right intercarpal joint.
- Horses were treated with varying doses (10, 20, 40mg) of the NSAID bufexamac, or sterile saline solution as a control, after one and two weeks of arthritis induction.
- Synovial fluid (SF) was sampled prior to induction and weekly for five weeks thereafter. This fluid was studied to determine levels and activity of Matrix Metalloproteinases (MMP-2, -8, -9).
- MMP activity was analyzed using gelatin zymography (for MMP-2 and MMP-9) and Western Blotting for MMP-8.
Key Results
- Injection of amphotericin B led to notable increases in the activity levels of MMP-2, -8, and -9. MMP-2 showed the most significant increase.
- MMP-9 levels returned to their normal state within 2 weeks, but MMP-2 levels remained high even after 5 weeks.
- The treatment with bufexamac didn’t significantly change the levels of the gelatinolytic MMP.
Important Conclusions
- The research suggests that an acute arthritis condition in horses leads to an elevated MMP activity within the joint for several weeks. Additionally, this potent activity could promote cartilage degradation.
- The NSAID bufexamac did not appear to substantially alter this condition.
- Further, the study proposes that analyzing the activity level of MMP-9 and especially the active forms of MMP-2 could be a useful predictive marker for the onset of arthritis in horses.
The researchers conclude that while the NSAID bufexamac does not significantly impact these enzyme levels, it might have the potential to predict the onset of arthritis, which could be a vital tool in equine health management.
Cite This Article
APA
Marttinen PH, Raulo SM, Suominen MM, Tulamo RM.
(2006).
Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac.
J Vet Med A Physiol Pathol Clin Med, 53(6), 311-318.
https://doi.org/10.1111/j.1439-0442.2006.00837.x Publication
Researcher Affiliations
- Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, 00014 HU, Finland. piia.marttinen@helsinki.fi
MeSH Terms
- Amphotericin B / toxicity
- Animals
- Anti-Inflammatory Agents / therapeutic use
- Bufexamac / therapeutic use
- Female
- Horse Diseases / drug therapy
- Horse Diseases / enzymology
- Horses
- Male
- Matrix Metalloproteinase 2 / metabolism
- Matrix Metalloproteinase 8 / metabolism
- Matrix Metalloproteinase 9 / metabolism
- Random Allocation
- Synovial Fluid / chemistry
- Synovitis / drug therapy
- Synovitis / enzymology
- Synovitis / veterinary
- Treatment Outcome
Citations
This article has been cited 4 times.- Barton AK, Richter IG, Ahrens T, Merle R, Alalwani A, Lilge S, Purschke K, Barnewitz D, Gehlen H. MMP-9 Concentration in Peritoneal Fluid Is a Valuable Biomarker Associated with Endotoxemia in Equine Colic. Mediators Inflamm 2021;2021:9501478.
- Barrachina L, Remacha AR, Romero A, Vitoria A, Albareda J, Prades M, Roca M, Zaragoza P, Vázquez FJ, Rodellar C. Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis. BMC Vet Res 2018 Aug 17;14(1):241.
- Ma TW, Li Y, Wang GY, Li XR, Jiang RL, Song XP, Zhang ZH, Bai H, Li X, Gao L. Changes in Synovial Fluid Biomarkers after Experimental Equine Osteoarthritis. J Vet Res 2017 Dec;61(4):503-508.
- Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 2011 Nov 15;12:259.
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