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Cell Tissue Res ; 340(1): 179-88, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20217136

RESUMO

Pro-inflammatory cytokines induce meniscal matrix degradation and inhibition of endogenous repair mechanisms, but the pathogenic mechanisms behind this are mostly unknown. Therefore, we investigated details of interleukin-1 (IL-1alpha)-induced aggrecan turnover in mature meniscal tissue explants. Fibro-cartilagenous disks (3 mm diameter x 1 mm thickness) were isolated from the central, weight-bearing region of menisci from 2-year-old cattle. After 3 or 6 days of IL-1alpha-treatment, GAG loss (DMMB assay), biosynthetic activity ([(35)SO(4)]-sulfate and [(3)H]-proline incorporation), gene expression (quantitative RT-PCR) and the abundance (zymography, Western blot) of matrix-degrading enzymes and specific aggrecan products were determined. Meniscal fibrocartilage had a 4-fold lower GAG content (per wet weight) than adjacent articular cartilage, and expressed MMPs-1, -2, -3 and ADAMTS4 constitutively, whereas ADAMTS5 m-RNA was essentially undetectable. Significant IL-1 effects were a decrease in biosynthetic activity, an increase in GAG release and in the expression/abundance of MMP-2, MMP-3 and ADAMTS4. Fresh tissue contained aggrecan core protein products similar to those previously described for bovine articular cartilage of this age. IL-1 induced the release of aggrecanase-generated CS-substituted products including both high (>250 kDa) and low molecular weight (about 75 kDa) species. TIMP-3 (but not TIMP-1 and -2 or a broad spectrum MMP inhibitor) inhibited IL-1-dependent GAG loss. In addition, IL-1 induced the release of preformed pools of three known G1-bearing products. We conclude that aggrecanases are responsible for IL-1-stimulated GAG release from meniscal explants, and that IL-1 also stimulates release of G1-bearing products, by a process possibly involving hyaluronan fragmentation.


Assuntos
Agrecanas/metabolismo , Artrite/imunologia , Glicosaminoglicanos/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1alfa/metabolismo , Meniscos Tibiais/imunologia , Proteínas ADAM/efeitos dos fármacos , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAMTS4 , Agrecanas/efeitos dos fármacos , Animais , Artrite/metabolismo , Artrite/fisiopatologia , Calpaína/efeitos dos fármacos , Calpaína/genética , Calpaína/metabolismo , Bovinos , Endopeptidases/efeitos dos fármacos , Endopeptidases/genética , Endopeptidases/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Ácido Hialurônico/metabolismo , Mediadores da Inflamação/farmacologia , Interleucina-1alfa/farmacologia , Metaloproteinases da Matriz/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Meniscos Tibiais/efeitos dos fármacos , Meniscos Tibiais/metabolismo , Modelos Biológicos , Pró-Colágeno N-Endopeptidase/efeitos dos fármacos , Pró-Colágeno N-Endopeptidase/genética , Pró-Colágeno N-Endopeptidase/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Inibidor Tecidual de Metaloproteinase-3/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo
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