Gendron Christi, Kashiwagi Masahide, Hughes Clare, Caterson Bruce, Nagase Hideaki
Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, W6 8LH, London, UK.
FEBS Lett. 2003 Dec 18;555(3):431-6. doi: 10.1016/s0014-5793(03)01295-x.
Aggrecanases are considered to play a key role in the destruction of articular cartilage during the progression of arthritis. Here we report that the N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3 (N-TIMP-3), but not TIMP-1 or TIMP-2, inhibits glycosaminoglycan release from bovine nasal and porcine articular cartilage explants stimulated with interleukin-1alpha or retinoic acid in a dose-dependent manner. This inhibition is due to the blocking of aggrecanase activity induced by the catabolic factors. Little apoptosis of primary porcine chondrocytes is observed at an effective concentration of N-TIMP-3. These results suggest that TIMP-3 may be a candidate agent for use against cartilage degradation.
在关节炎进展过程中，聚集蛋白聚糖酶被认为在关节软骨破坏中起关键作用。在此我们报告，金属蛋白酶组织抑制剂3的N端抑制结构域（N-TIMP-3），而非TIMP-1或TIMP-2，以剂量依赖方式抑制白细胞介素-1α或视黄酸刺激的牛鼻和猪关节软骨外植体中糖胺聚糖的释放。这种抑制是由于阻断了分解代谢因子诱导的聚集蛋白聚糖酶活性。在N-TIMP-3的有效浓度下，未观察到原代猪软骨细胞有明显凋亡。这些结果表明，TIMP-3可能是一种用于对抗软骨降解的候选药物。
