Treadwell B V, Pavia M, Towle C A, Cooley V J, Mankin H J
Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114.
J Orthop Res. 1991 May;9(3):309-16. doi: 10.1002/jor.1100090302.
The work described here demonstrates the synthesis by human articular cartilage of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of the serine protease tissue plasminogen activator (tPA). We also present data demonstrating an increase in PAI-1 messenger ribonucleic acid (mRNA) in chondrocytes exposed to the cytokine interleukin-1 (IL-1). Interestingly, this elevation of steady-state mRNA levels does not appear to result in an increase in synthesis of PAI-1 protein. Northern blot analysis reveals that of the two mRNA species (3.4 kb, 2.4 kb) previously reported for PAI-1, only the larger species (3.4 kb) appears to be synthesized by chondrocytes. Our data demonstrate the IL-1-stimulated production by cartilage of tissue plasminogen activator. We also show evidence for the presence of plasminogen in cartilage. A scheme is presented indicating the probable importance of the serine proteases (tPA and plasminogen) and PAI-1 in cartilage degradation.
本文所述工作证明了人关节软骨可合成纤溶酶原激活物抑制剂-1(PAI-1),它是丝氨酸蛋白酶组织纤溶酶原激活物(tPA)的一种强效抑制剂。我们还展示了数据,表明暴露于细胞因子白细胞介素-1(IL-1)的软骨细胞中PAI-1信使核糖核酸(mRNA)增加。有趣的是,这种稳态mRNA水平的升高似乎并未导致PAI-1蛋白合成增加。Northern印迹分析显示,先前报道的PAI-1的两种mRNA种类(3.4 kb、2.4 kb)中,只有较大的种类(3.4 kb)似乎是由软骨细胞合成的。我们的数据证明了IL-1刺激软骨产生组织纤溶酶原激活物。我们还展示了软骨中存在纤溶酶原的证据。提出了一个示意图,表明丝氨酸蛋白酶(tPA和纤溶酶原)和PAI-1在软骨降解中的可能重要性。