Oct 1, 1976

Metalloproteases of human articular cartilage that digest cartilage proteoglycan at neutral and acid pH

The Journal of Clinical Investigation
A I SapolskyJ F Woessner

Abstract

Extracts of human articular cartilage contain proteases capable of degrading the proteoglycan component of cartilage matrix at neutral and acid pH. These enzymes have been partially purified by ion exchange chromotography and characterized by disc electrophoresis, inhibition patterns, and action of proteoglycan. Three distinct metalloproteases are described. A neutral protease that digests proteoglycan subunit optimally at pH 7.25 has been purified up to 900-fold. It is strongly inhibited by o-phenanthroline, alpha-2-macroglobulin, and egg white, and to a lesser extent by D-penicillamine and EDTA. Inhibition by chelating agents is reversed by cobalt, zinc, and ferrous ions. Two acid metalloproteases, distinct from cathespins B1, D, and F, digest proteoglycan subunit at pH 4.5 and 5.5. Both are inhibited by o-phenanthroline and activity is restored by cobalt, zinc, or ferrous ions. With electron microscopy, it was found that cartilage slices were depleted of ruthenium red-staining matrix proteoglycan after incubation in vitro with a partially purified cartilage extract at neutral pH. Sedimentation, gel chromatography, sodium dodecyl sulfate-gel electrophoresis, and immuno-diffusion studies of digests of isolated proteoglycan fra...Continue Reading

Mentioned in this Paper

Glycosaminoglycans
Structure of Articular Cartilage
Peptide Hydrolases
Electrophoresis, Disc
A2M
Ion-Exchange Chromatography Procedure
Histone H7
Molecular Sieve Chromatography
Immunodiffusion Measurement
Hydrogen-Ion Concentration

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