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1.
Braz. j. med. biol. res ; 50(4): e5714, 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-839285

RESUMEN

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.


Asunto(s)
Animales , Masculino , Antiinflamatorios/farmacología , Artralgia/enzimología , Condrocitos/enzimología , Flavanonas/farmacología , Articulación de la Rodilla/enzimología , Metaloproteinasa 3 de la Matriz/biosíntesis , Osteoartritis de la Rodilla/enzimología , Artralgia/tratamiento farmacológico , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Modelos Animales de Enfermedad , Expresión Génica , Interleucina-1beta/análisis , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/metabolismo , Articulación de la Rodilla/patología , Metaloproteinasa 3 de la Matriz/análisis , FN-kappa B/análisis , FN-kappa B/efectos de los fármacos , Inhibidor NF-kappaB alfa/análisis , Inhibidor NF-kappaB alfa/efectos de los fármacos , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/patología , Distribución Aleatoria , Ratas Wistar , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Resultado del Tratamiento
2.
Biol. Res ; 48: 1-8, 2015. ilus, graf, tab
Artículo en Inglés | LILACS | ID: biblio-950828

RESUMEN

BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.


Asunto(s)
Humanos , Animales , Masculino , Femenino , Adolescente , Persona de Mediana Edad , Anciano , Ratones , Ratas , Adulto Joven , Quimiocina CCL2/metabolismo , Condrocitos/metabolismo , Osteoartritis de la Rodilla/fisiopatología , Receptores CCR2/metabolismo , Membrana Sinovial/citología , Técnicas In Vitro , Ensayo de Inmunoadsorción Enzimática , Ratas Sprague-Dawley , Apoptosis/fisiología , Progresión de la Enfermedad , Quimiocina CCL2/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Condrocitos/enzimología , Ácido Yodoacético , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Metaloproteinasa 13 de la Matriz/metabolismo , Receptores CCR2/antagonistas & inhibidores , Receptores CCR2/genética , Fibroblastos/metabolismo , Proteínas Matrilinas/metabolismo , Ratones Endogámicos C57BL
3.
Braz. j. med. biol. res ; 44(12): 1231-1242, Dec. 2011. ilus, tab
Artículo en Inglés | LILACS | ID: lil-606547

RESUMEN

The mitogenic effects of periodic mechanical stress on chondrocytes have been studied extensively but the mechanisms whereby chondrocytes sense and respond to periodic mechanical stress remain a matter of debate. We explored the signal transduction pathways of chondrocyte proliferation and matrix synthesis under periodic mechanical stress. In particular, we sought to identify the role of the MEK1/2-ERK1/2 signaling pathway in chondrocyte proliferation and matrix synthesis following cyclic physiologic mechanical compression. Under periodic mechanical stress, both rat chondrocyte proliferation and matrix synthesis were significantly increased (P < 0.05) and were associated with increases in the phosphorylation of Src, PLCγ1, MEK1/2, and ERK1/2 (P < 0.05). Pretreatment with the MEK1/2-ERK1/2 selective inhibitor, PD98059, and shRNA targeted to ERK1/2 reduced periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis (P < 0.05), while the phosphorylation levels of Src-Tyr418 and PLCγ1-Tyr783 were not inhibited. Proliferation, matrix synthesis and phosphorylation of MEK1/2-Ser217/221 and ERK1/2-Thr202/Tyr204 were inhibited after pretreatment with the PLCγ1 inhibitor U73122 in chondrocytes in response to periodic mechanical stress (P < 0.05), while the phosphorylation site of Src-Tyr418 was not affected. Inhibition of Src activity with PP2 and shRNA targeted to Src abrogated chondrocyte proliferation and matrix synthesis (P < 0.05) and attenuated PLCγ1, MEK1/2 and ERK1/2 activation in chondrocytes subjected to periodic mechanical stress (P < 0.05). These findings suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis in part through the Src-PLCγ1-MEK1/2-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade.


Asunto(s)
Animales , Ratas , Condrocitos/citología , Condrocitos/enzimología , Sistema de Señalización de MAP Quinasas/fisiología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Estrés Mecánico , Sistema de Señalización de MAP Quinasas/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Mitógenos/metabolismo , Fosfolipasa C gamma/metabolismo , Ratas Sprague-Dawley , Familia-src Quinasas/metabolismo
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