Lysosomal elastase: effect on mechanical and biochemical properties of normal cartilage, inhibition by polysulfonated glycosaminoglycan, and binding to chondrocytes.
Rheumatic joint destruction usually starts with the destabilisation of cartilage. Lysosomal elastase is a candidate effector of this process, since this enzyme is found at the site of cartilage erosion by rheumatoid synovial tissue. In order to prove this hypothesis we assessed the mechanical stability of cartilage during treatment by this enzyme in vitro. An indentation apparatus was used for this purpose and biochemical as well as microscopic techniques were used to supplement the results thus obtained. Our findings show that elastase irreversibly impairs the stability of cartilage by lysis of matrix proteoglycans without the help of additive enzymes. Collagen fragmentation played no significant role during elastase-induced destabilisation, while specific collagenase attacked the collagen network within the matrix only subsequent to the removal of proteoglycans. These findings suggest that elastase is a leading enzyme during proteolytic cartilage degradation. In addition polysulfonated glycosaminoglycan was found to reduce the mechanical effect of elastase on normal cartilage. It is therefore concluded that local inhibition of elastase promises therapeutic benefit during rheumatic cartilage degradation. Upon treatment of cartilage with elastase we observed this enzyme not only within the matrix under destruction but also bound to chondrocytes. These findings support the hypothesis that elastase plays a role on the matrix not only by direct degradation, but also by an indirect effect mediated through living chondrocytes.
D000293:Adolescent; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001673:Biodegradation, Environmental / Q000187:drug effects; D001696:Biomechanical Phenomena; D001857:Bone Matrix / Q000201:enzymology; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes; D008247:Lysosomes / Q000201:enzymology*; D003012:Microbial Collagenase / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D013696:Temperature
D006025:Glycosaminoglycans; D011509:Proteoglycans; C013786:A73025; D003094:Collagen; D010196:Pancreatic Elastase; D003012:Microbial Collagenase