A putative role for cathepsin K in degradation of AA and AL amyloidosis

The aims of this study were to investigate the role of cathepsin K in the p athology of amyloidosis by demonstrating its presence in multinucleated gia nt cells (MGCs) adjacent to amyloid deposits, and determining its ability t o degrade amyloid fibril proteins tn vitro. The study was performed using a utopsy and biopsy specimens from patients with AA. or AL amyloidosis. In si x (55%) patients with AA amyloidosis and seven (58%) patients with AL amylo idosis, variable numbers of CD68-immunoreactive MGCs were found adjacent to amyloid deposits. In each case strong cytoplasmic immunostaining for cathe psin K was found in MGCs; immunostaining of amyloid deposits was present in five (45%) patients with AA amyloidosis and three (25%) patients with AL a myloidosis. In vitro degradation experiments showed that recombinant cathep sin K completely degraded AA amyloid fibril proteins at pH 5.5 as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blott ing. Less effective degradation took place at pH 7.4 and there was no degra dation in the presence of a general cysteine protease inhibitor (E64) or in the absence of cathepsin K. This is the first study to show that cathepsin K is expressed in MGCs adjacent to amyloid deposits and to demonstrate its ability to degrade amyloid fibril proteins.