Le rôle du cytosquelette dans la mécanique des cellules du cartilage, les chondrocytes

This study is based on the hypothesis that in situ cytoskeleton structure and composition vary with depth in mature articular cartilage. Thus, the first objective consisted of the examination of the three-dimensionnal organisation of the chondrocyte cytoskeleton networks in situ

The second objective of this study consisted of the examination of the distribution of the three cytoskeletal networks as a function of depth in mature articular cartilage. The heterogeneous content of cytoskeleton components in the different cartilage zones, as observed by epifluorescence microscopy and SDS-PAGE, suggested a microenvironnemental regulation of cytoskeleton expression.

We observed that high speed dynamic compression affected the cytoskeleton organisation, notably by transforming a normally punctuated actin labelling into a more diffuse one. These tests also allowed us to note that vimentin Ser82 phosphorylation pattern was modified differentially according to the applied compression type.

Mechanical studies were performed to understand the character of cartilage response to compressions. The mechanical aspect of this thesis focused on the characterisation of the mechanical behaviour of articular cartilage for loading conditions similar to those used in the biological study. The transient response of adult articular cartilage was found to be non-linear, initially weakening and then significantly stiffening with increasing deformation. It also showed sensitivity to strain rate, its stiffening being more significant at high than at low compression speed.

The cytoskeleton study revealed the organisation and distribution of the three cytoskeletal proteins and presented cytoskeleton organisation changes in response to various mechanical stimuli. The examination of vimentin phosphorylation changes, for its part, constitutes the first study of this type. Concerning the mechanical analysis, this is the only study focussing on the linearity/nonlinearity of the articular cartilage response to finite deformation applied in unconfined compression, and the only one to examine the dependence of linearity on strain rate. Furthermore, the testing protocol designed for this experiment is unique since it allows for determination of a critical deformation level where material mechanical property degradation begins. All of this new information is essential for the comprehension of articular cartilage mechanics and function in physiological situations as well as in the comprehension of osteoarthritis etiology and pathogenesis. (Abstract shortened by UMI.)