Nicolás Caggiano

Efecto del alendronato sobre el perfil de citoquinas y metaloproteinasas 2 y 9 en un modelo múrido de artritis experimental

Resumen Introduccion La artritis es una de las artropatias mas frecuentes, se caracteriza por el dano que produce en el cartilago articular y la resorcion osea subcondral. El diagnostico temprano es de crucial importancia para instaurar una terapia preventiva, ya que, en ocasiones, la enfermedad es diagnosticada al presentarse lesiones oseas de dificil resolucion. Objetivos Caracterizar, en un modelo murido de artritis experimental producida por adyuvante, el perfil de distintos biomarcadores articulares, interleuquinas (IL-4, IL-6 y TNF-α) y metaloproteasas (MMP-2 y MMP-9), que permitan seguir la evolucion de la enfermedad y analizar sus diferencias, al aplicar el tratamiento con alendronato en forma preventiva o curativa. Materiales y metodos El alendronato, en forma preventiva, se aplico el dia 0 y de manera curativa a los dos meses posadyuvante. Se realizo un puntaje de los sintomas clinicos; al sacrificio, se determinaron los marcadores articulares y se realizaron los estudios histopatologicos y radiograficos. Resultados Lo mas destacable fue que el grupo que recibio el alendronato, de manera preventiva, alcanzo un puntaje clinico normal de manera mas temprana que el grupo control con adyuvante. Asimismo, los animales tratados con alendronato presentaron valores significativamente mas bajos de metaloproteasas. Conclusiones Nuestros resultados sugieren que, aparentemente, el alendronato disminuye la actividad de proteasas vinculadas a la fisiopatologia de la enfermedad articular, lo cual podria resultar sumamente beneficioso para la terapeutica a instaurar.

Determination of reference values for cytokines and matrix metalloproteinases in the synovial fluid of horses of different ages

Osteoarthritis (OA) is the most common joint disease in sport horses. Inflammatory and anti-inflammatory cytokines and metalloproteinases (MMPs) play a crucial role in the degradation of the cartilage extracellular matrix. The study of inflammatory molecular biomarkers could be useful in the diagnosis and choice of therapeutic strategies. However, little is known about the normal values of inflammatory biomarkers at different ages. Moreover, early diagnosis of OA is crucial to ensure early treatment in order to prevent chronic damage. The aim of this study was to establish a reference range for values of pro-inflammatory cytokines (IL-1β, IL-4, IL-6 and TNF-α) and MMPs (MMP-2 and MMP-9) in the synovial fluid of horses of different ages. The old horses group presented higher values of IL-4 and TNF-α than the rest of the groups studied (P<0.001 vs. all other groups). IL-1β levels were higher in foals than in all the other groups (P<0.001). No statistically significant differences were found between the groups as regards the mean IL-6 values. Synovial MMP-2 levels were statistically lower in the old horses group (P<0.001) and higher in the foals group (P<0.05). Higher MMP-9 levels were found in the foals group (55.45 ± 58.1 percentage of proteolysis) (P<0.001 vs. all other groups). This study demonstrates the existence of variations in the levels of pro-inflammatory markers in the synovial fluid of horses at different ages.

Pamidronate effects in horse osteoarthritis: Relationship of clinical score with inflammatory biomarkers in synovial fluid

Introduction: The use of pamidronate in horses with OA could prevent resorptive phenomena associated with joint disease, and may reduce the inflammatory process and resulting pain. Objective was to analyze differences in clinical scores in horses with osteoarthritis before and after the treatment with pamidronate and standardized correlation with the protein profile and inflammatory markers (IL-6, TNF-α, MMP-2 and MMP-9).Materials and methods: Inflammation markers of synovial fluid from clinically healthy horses (clinical score ≤ 4), and patients (n = 5) (clinical score N 5–9) were evaluated basal and days 3, 10 and 21 after treatment. On day 0 and day 2 intravenous pamidronate (90 mg) were applied to the sick horses. IL-6 and TNF-α were assessed by ELISA; MMP-2 and 9 were evaluated by zymography. Changes in synovial fluid protein profile of pre and post treatment were evaluated by SDS-PAGE. Direct BP inhibition on MMP-9 activity in vitro was determined by zymography. Results: IL-6 did not show significant difference, TNF-α; increased at day 21 post treatment, differences were observed between healthy group and “day 3” (p b 0.001) and “untreated patients” (p b 0.01). For MMP-2 p= ns and MMP-9 showed significant individual differences after the second dose And in protein profile study, before and after treatment, no significant differences were observed. Conclusion: Pamidronate reduced MMP-9 activity. Protease was involved in the degenerative and inflammatory processes by degrading the extracellular matrix, but no direct inhibition on MMP-9 occurred. For TNF-α, the increased may be associated with a certain exacerbation of the inflammatory process which can be considered as beneficial to the resolution of chronic arthritis.