Sulfated glucosamine inhibits MMP-2 and MMP-9 expressions in human fibrosarcoma cells.
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.
Rajapakse
Niranjan
N
Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, South Korea.
Mendis
Eresha
E
Kim
Moon-Moo
MM
Kim
Se-Kwon
SK
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000737:chemistry* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D016328:NF-kappa B; D011480:Protease Inhibitors; D013431:Sulfates; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005944:Glucosamine