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Biomedical and Environmental Sciences ; (12): 277-283, 2013.
Article Dans Anglais | WPRIM | ID: wpr-320341

Résumé

<p><b>OBJECTIVE</b>To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).</p><p><b>METHODS</b>Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.</p><p><b>RESULTS</b>It was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.</p><p><b>CONCLUSION</b>NF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.</p>


Sujets)
Sujet âgé , Femelle , Humains , Adulte d'âge moyen , Apoptose , Acides caféiques , Pharmacologie , Utilisations thérapeutiques , Calcium , Physiologie , Cellules cultivées , Chondrocytes , Sécrétions corporelles , Évaluation préclinique de médicament , Matrix metalloproteinase 2 , Métabolisme , Matrix metalloproteinase 9 , Métabolisme , Facteur de transcription NF-kappa B , Arthrose , Traitement médicamenteux , Alcool phénéthylique , Pharmacologie , Utilisations thérapeutiques , Facteur de nécrose tumorale alpha , Pharmacologie
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