Rajapakse Niranjan, Mendis Eresha, Kim Moon-Moo, Kim Se-Kwon
Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, South Korea.
Bioorg Med Chem. 2007 Jul 15;15(14):4891-6. doi: 10.1016/j.bmc.2007.04.048. Epub 2007 Apr 29.
In the present study, sulfated glucosamine (SGlc) that has been reported to relieve joint pain and inflammation in many arthritis patients was studied for its inhibitory effects on MMP-2 and MMP-9 in human fibrosarcoma cells. Expression and activity of above MMPs studied using gelatin zymography suggested SGlc as a potent MMP inhibitor. Further, transfection of promoter genes of MMPs and their transcription factors clearly exhibited that inhibition of MMP-2 and MMP-9 was due to down-regulation of transcription factor, NF-kappaB. However expression of activator protein-1 (AP-1), another important transcription factor of MMPs, was not affected by SGlc treatment. In addition, protein expression results of Western blot analysis were also in agreement with the results of gene transfection experiments. Moreover, down-regulation of NF-kappaB resulted in production of low levels of both NF-kappaB p50 and p65 proteins and directly affected activation process of MMP-2 and MMP-9 expressions. Since MMPs involve in joint inflammation, it can be presumed that inhibition of MMP-2 and MMP-9 can be one of the mechanisms of SGlc to be an effective drug in relieving the symptoms of osteoarthritis.
在本研究中，对已报道可缓解许多关节炎患者关节疼痛和炎症的硫酸氨基葡萄糖（SGlc），研究了其对人纤维肉瘤细胞中基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的抑制作用。使用明胶酶谱法对上述基质金属蛋白酶的表达和活性进行研究，结果表明SGlc是一种有效的基质金属蛋白酶抑制剂。此外，对基质金属蛋白酶及其转录因子的启动子基因进行转染，结果清楚地显示对MMP-2和MMP-9的抑制是由于转录因子核因子κB（NF-κB）的下调。然而，MMPs的另一个重要转录因子激活蛋白-1（AP-1）的表达不受SGlc处理的影响。此外，蛋白质印迹分析的蛋白质表达结果也与基因转染实验的结果一致。此外，NF-κB的下调导致NF-κB p50和p65蛋白水平均较低，并直接影响MMP-2和MMP-9表达的激活过程。由于基质金属蛋白酶参与关节炎症，因此可以推测抑制MMP-2和MMP-9可能是SGlc成为缓解骨关节炎症状的有效药物的机制之一。
