Résumé
INTRODUCTION: Articular cartilage is a connective tissue, composed of chondrocytes and an extracellularmatrix, rich in collagens and proteoglycans 1. The main biological function of articular cartilage is to permitfrictionless movements of the connected bones while facilitating force transmission. Cartilage thereforeexhibits a sufficient rigidity to resist mechanical loading and absorbs a part of the contact energy between therelated bones. However, articular cartilage is a non-vascularized tissue with limited self-healing and repaircapacities. With aging and disease, articular cartilage fails to respond to biomechanical stimuli resulting inimpaired capacity of regeneration. Better understanding the processes of mechanotransduction and cartilagegrowth will speed up the improvement of tissue engineering approaches. The aim of this study is to set up acompression device to measure biomechanical properties of cartilage micropellets in different conditions tohave a modelisation of cartilage growth.METHODS: In the present study, we used the in vitro model of cartilage micropellets obtained from thedifferentiation of human mesenchymal stem cells (MSC) into chondrocytes by 3D-culture in presence of theinducing factor TGFβ3 2. These cartilage micropellets were submitted to mechanical loading (i.e., compressiontests by using a home-made compression device) and biochemical analysis (i.e., RT-qPCR andimmunocytochemistry) after respectively 7, 14, 21, 29 and 35 days of cell differentiation.RESULTS: This cross analysis showed that micropellets generated with TGFβ3 exhibit a significant higherYoung’s modulus and disspated energy than undifferentiated micropellets (generated without TGFβ3). Thesedata reflected the visco-elastic mechanical properties of micropellets that are close to those of human nativearticular cartilage. In particular, the elasticity modulus felt into the range of values obtained by using AFM onnon-degraded articular cartilage at nanometer scale (i.e., actually 150 kPa vs 83 kPa3). Interestingly, we couldnot measure the mechanical properties of micropellets during the two first weeks of culture where productionof the cartilage matrix components was low. The Young’s modulus and the dissipated energy both increasedfrom day 14 to day 29 in parallel to the increase of chondrocyte gene expression. Finally, the mechanicalproperties were highly correlated with gene expression levels of type II collagen and LINK protein.DISCUSSION & CONCLUSIONS: The present results confirm that MSC-derived cartilage micropelletsare a relevant in vitro model devoted to mechanobiological and biomechanical studies of cartilage growth.