Cytoskeletal architecture and cathepsin B trafficking in human articular chondrocytes.
In the differentiated state, human articular chondrocytes exhibited modestly developed cytoskeletal components, while cells dedifferentiated by serial subcultures in vitro displayed a prominent cytoskeleton. Morphological changes, a well-developed actin cytoskeleton, and the presence of numerous intracellular organelles were characteristic features of the dedifferentiated chondrocyte phenotype. These properties correlated with the expression, biosynthesis, storage, and secretion of the cysteine peptidase, cathepsin B, a marker of the dedifferentiated chondrocyte phenotype and a potent mediator of cartilage catabolism in osteoarthritis. Both the actin cytoskeleton and microtubules were responsible for trafficking of cathepsin B between cellular compartments in chondrocytes. Despite the endosomes and lysosomes storing high amounts of mature cathepsin B, this enzyme could not be visualized in its active form within these organelles. However, enzymatically active cathepsin B was associated with polymerized tubulin, and was no longer detectable after disruption of the microtubules. This enzyme species possibly represents the mature cathepsin B form in transport vesicles, after cleavage of the inhibitory propeptide, on the way to a final target. These results suggest noteworthy parallels between osteoarthritic articular cartilage and the artificially dedifferentiated cell phenotype, including the expression of type I collagen, the expression of cathepsin B, a significant modification of the cytoskeleton, and the formation of abundant secretory vesicles. These similarities justify the use of chondrocyte cultures as models of the behavior of cartilage cells in osteoarthritis.
Zwicky
R
R
Center for Experimental Rheumatology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Baici
A
A
D015703:Antigens, CD / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D003094:Collagen; D002401:Cathepsin B