A single intraarticular injection of a tranexamic acid-modified hyaluronic acid (HA/TXA) alleviates pain and reduces OA development in a murine model of monosodium iodoacetate-induced osteoarthritis.
| Autor: | Brochard S; UR7451 Bioconnect, Université de Caen Normandie, Caen, France., Boumédiene K; UR7451 Bioconnect, Université de Caen Normandie, Caen, France., Mercier J; Laboratoire de Rhumatologie Appliquée, Lyon, France., Agin V; INSERM U1237, Physiopathology and Imaging of Neurological Disorders, Université de Caen Normandie, Caen, France., Conrozier T; Department of Rheumatology, Hôpital Nord Franche-Comté, Belfort, France., Baugé C; UR7451 Bioconnect, Université de Caen Normandie, Caen, France. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Frontiers in pharmacology [Front Pharmacol] 2024 Sep 11; Vol. 15, pp. 1456495. Date of Electronic Publication: 2024 Sep 11 (Print Publication: 2024). |
| DOI: | 10.3389/fphar.2024.1456495 |
| Abstrakt: | Rationale: Tranexamic acid (TXA) is a strong and specific plasminogen activator inhibitor with inhibitory effects on the matrix metalloproteases involved in the pathophysiology of osteoarthritis (OA) through targeting of the fibrinolysis pathway. In this study, we evaluated the analgesic and chondroprotective effects of a HA-tranexamic acid (HA/TXA) conjugate, compared to HA alone and placebo, in an animal model of knee OA. Methods: Knee OA was induced in 15 C 5 7 b l/6J mice by IA injection of 0.75 mg of Monosodium IodoAcetate (MIA). At day 28, the mice received 1 IA injection of 10 µL of saline (control-group), or of HA or of HA/TXA. Tactile sensitivity was assessed using von Frey filaments. Stimulations started at 1 g and increased until a response was obtained (up to 4 g). A response to the stimulus was counted if the animal withdrew its paw. If the animal responded to the 1 g stimulation, stimulation was reduced until the lack of response was observed (up to 0.2 g). At day 56, mice were euthanized for knee histological assessment. Cartilage degradation was assessed using the OARSI score. Statistical analysis was performed on GraphPad Prism 8.0.2 software. Kruskal-Wallis or Mann-Whitney tests were performed as appropriate. Results: Just before treatment administration, no intergroup difference in paw withdrawal threshold was observed. Throughout the experiment animals given saline and HA had a lower paw withdrawal threshold than those treated with HA/TXA ( p < 0.01). In the control group OARSI score was 5.5 ± 0.6. In HA and HA + TXA treated mice the OARSI score was 3.2 ± 0.8 and 3.1 ± 0.5 ( p < 0.01) showing that both treatments were able to reduce OA progression. Conclusion: In this animal model of MIA induced KOA, a single IA injection of a HA/TXA conjugate resulted in a greater efficacy on pain than both saline and HA. HA and HA/TXA exhibited chondroprotective effects compared to placebo. Competing Interests: Jeromine mercier is a employee of LABRHA TC received honoraria from LABRHA for scientific and consulting services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Brochard, Boumédiene, Mercier, Agin, Conrozier and Baugé.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|