Glucosamine sulfate suppresses the expressions of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis

Background: Glucosamine sulfate may have an ex vivo inhibitory effect on the plasminogen activator (PA)/plasmin system and gelatinases expression during the early development of osteoarthritis (OA). Methods: We compared the levels of urokinase-type PA (u-PA), PA inhibitor-1 (PAI-1) and gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and -9]) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without glucosamine sulfate. Results: Gelatin zymography revealed that glucosamine sulfate could suppress MMP-2 secretion in chondral, meniscal and synovial cultures and also decrease MMP-9 production in synovial and meniscal cultures. ELISA data also showed the suppressive effects of glucosamine sulfate on u-PA and PAI-1 production in synovial cultures at 48 h. Conclusions: Our data suggest that one of the therapeutic effects of glucosamine sulfate is to down-regulate the expressions of u-PA, PAI-1, MMP-2 and MMP-9 that underlie the destruction of articular cartilage in the early stage of OA, and therefore to delay the joint failure.