[The enzymatic mechanisms involved in the pathogenesis of rheumatoid arthritis and arthrosis. The role of metalloproteases and serine proteases in the breakdown of articular cartilage].
Rheumatoid arthritis and osteoarthritis, expression, respectively, of inflammatory and degenerative articular involvement, are the most important diseases affecting joint cartilage. Proteolytic enzymes are the effectors of the articular damage: their increased production by chondrocytes and synoviocytes leads to cartilage breakdown. These enzymes, whose structure and specific activities have been defined in the recent years, carry out their action in the extracellular matrix. They are characterized by the presence of a particular element at the active site, that allows to distinguish four different families. The most studied and the best known among them are metalloproteinases, represented by several enzymes with common features, and serinoproteinases, some members of which, particularly urokinase and tissue-type plasminogen activator, are recently indicated as potential responsible for articular destruction. Activators, and inhibitors of proteinases play a fundamental role: a fine balance, that controls the mechanisms of activation and inhibition, seems to take place at transcriptional level. Any factor able to modify the cellular shape and the cytoskeleton, gives rise to lytic enzyme expression at the genomic level. With the progress of knowledges, serinoproteinases are assuming an increasing relevance, particularly the components of the fibrinolytic pathway.
Lombardi
A
A
Istituto di Clinica Medica IV, Università, Firenze.
Pignone
A
A
Perfetto
F
F
Tarquini
R
R
Partsch
G
G
Matucci-Cerinic
M
M
D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000209:etiology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010003:Osteoarthritis / Q000201:enzymology* / Q000209:etiology*; D010960:Plasminogen Activators / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity
D015842:Serine Proteinase Inhibitors; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases
I meccanismi enzimatici coinvolti nella patogenesi dell'artrite reumatoide e dell'artrosi. Ruolo delle metallo-proteasi e delle serino-proteasi nel deterioramento della cartilagine articolare.