Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage Report as inadecuate




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Arthritis Research and Therapy

, 14:R113

First Online: 14 May 2012Received: 11 November 2011Revised: 08 April 2012Accepted: 14 May 2012

Abstract

IntroductionThe intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis OA in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared.

MethodsFixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope C2K generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date.

ResultsIn most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid-deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix.

ConclusionsCleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.

AbbreviationsBSAbovine serum albumin

C2C and C12C: epitopes generated at the new C-terminus of type II collagen and types I and II collagen respectively following cleavage by collagenase in the triple helical region see Figure 1

C2Kepitope generated at a new C-terminal fragment of type II collagen following cleavage by cathepsin K

Col IItype II collagen

MMPmatrix metalloproteinase

OAosteoarthritis

PBSphosphate buffered saline

TC3-4 cleavage fragment generated on cleavage of the collagen molecule by the action of collagenases

Electronic supplementary materialThe online version of this article doi:10.1186-ar3839 contains supplementary material, which is available to authorized users.

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Author: Valeria M Dejica - John S Mort - Sheila Laverty - John Antoniou - David J Zukor - Michael Tanzer - A Robin Poole

Source: https://link.springer.com/







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