Early cathepsin K degradation of type II collagen in vitro and in vivo in articular cartilage

Abstract Objective To characterize the initial events in the of cleavage type II collagen mediated by cathepsin K and demonstrate the presence of the resulting products in human and equine articular osteoarthritic cartilage. Design Equine type II collagen was digested with cathepsin K and the cleava...

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Bibliographic Details
Published in:Osteoarthritis and cartilage 2016-08, Vol.24 (8), p.1461-1469
Main Authors: Mort, John S, Beaudry, Francis, Théroux, Kathleen, Emmott, Alexander A, Richard, Hélène, Fisher, William D, Lee, Eunice R, Poole, A. Robin, Laverty, Sheila
Format: Article
Language:English
Subjects:
Animals
Cartilage
Cartilage, Articular
Cathepsin K
Cattle
Collagen Type II
Collagenases
Horse
Horses
Humans
Neoepitope
Protease
Rheumatology
Type II collagen
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Summary:Abstract Objective To characterize the initial events in the of cleavage type II collagen mediated by cathepsin K and demonstrate the presence of the resulting products in human and equine articular osteoarthritic cartilage. Design Equine type II collagen was digested with cathepsin K and the cleavage products characterized by mass spectrometry. Anti-neoepitope antibodies were raised against the most N -terminal cleavage products and used to investigate the progress of collagen cleavage, in vitro , and the presence of cathepsin K-derived products in equine and human osteoarthritic cartilage. Results Six cathepsin K cleavage sites distributed throughout the triple helical region were identified in equine type II collagen. Most of the cleavages occurred following a hydroxyproline residue. The most N-terminal site was within three residues of the previously identified site in bovine type II collagen. Western blotting using anti-neoepitope antibodies showed that the initial cleavages occurred at the N-terminal sites and this was followed by more extensive degradation resulting in products too small to be resolved by SDS gel electrophoresis. Immunohistochemical staining of cartilage sections from equine or human osteoarthritic joints showed staining in lesional areas which was not observed in non-arthritic sites. Conclusions Cathepsin K cleaves triple helical collagen by erosion from the N-terminus and with subsequent progressive cleavages. The liberated fragments can be detected in osteoarthritic cartilage and may represent useful biomarkers for disease activity.
ISSN:1063-4584
1522-9653
DOI:10.1016/j.joca.2016.03.016