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Increase of TNFα-stimulated Osteoarthritic Chondrocytes Apoptosis and Decrease of Matrix Metalloproteinases 9 by NF-κB Inhibition 被引量:13

Increase of TNFα-stimulated Osteoarthritic Chondrocytes Apoptosis and Decrease of Matrix Metalloproteinases 9 by NF-κB Inhibition
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摘要 Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-KB 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). Methods Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFa-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants. Results 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 TNFa 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 TNFa for 24 h. The stimulatory effect of TNFa just on proMMP-9 was counteracted significantly by CAPE. Conclusion NF-KB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFa (a pro-apoptotic factor). Therefore, therapeutic NF-KB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9. Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-KB 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). Methods Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFa-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants. Results 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 TNFa 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 TNFa for 24 h. The stimulatory effect of TNFa just on proMMP-9 was counteracted significantly by CAPE. Conclusion NF-KB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFa (a pro-apoptotic factor). Therefore, therapeutic NF-KB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.
出处 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第4期277-283,共7页 生物医学与环境科学(英文版)
关键词 CHONDROCYTES GELATINASE APOPTOSIS NF-KB Tumor necrosis factor a Chondrocytes Gelatinase Apoptosis NF-KB Tumor necrosis factor a
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