caa a22 4500 47577437X CHVBK 20180406123626.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s004180000199 doi (NATIONALLICENCE)springer-10.1007/s004180000199 Cytoskeletal architecture and cathepsinB trafficking in human articular chondrocytes [Elektronische Daten] [Roman Zwicky, Antonio Baici] Abstract.: 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, cathepsinB, 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 cathepsinB between cellular compartments in chondrocytes. Despite the endosomes and lysosomes storing high amounts of mature cathepsinB, this enzyme could not be visualized in its active form within these organelles. However, enzymatically active cathepsinB was associated with polymerized tubulin, and was no longer detectable after disruption of the microtubules. This enzyme species possibly represents the mature cathepsinB 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 typeI collagen, the expression of cathepsinB, 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. Springer-Verlag, 2000 Chondrocytes CathepsinB Cytoskeleton Actin Tubulin Osteoarthritis nationallicence Zwicky Roman Center for Experimental Rheumatology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland aut Baici Antonio Center for Experimental Rheumatology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland aut https://doi.org/10.1007/s004180000199 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004180000199 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zwicky Roman Center for Experimental Rheumatology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland aut NATIONALLICENCE 700 1- Baici Antonio Center for Experimental Rheumatology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer