Structural and Mechanical Cues in Cartilage Morphogenesis

Abstract

The performance of most tissues crucially depends on their mechanical properties. Hyaline cartilage, such as articular cartilage (AC) or the growth plate (GP), shows a highly structured organization comprising different zones varying in their extracellular matrix (ECM) organization, composition and cellular arrangement. However, our current understanding of cartilage development is scarce regarding the influence of cartilage components on tissue specific structural and mechanical properties although proper cartilage function is pivotal for appropriate bone development and function.Therefore, the detection of mechanical changes and the possibility to image ECM structure simultaneously have important clinical relevance in the investigation of cartilage morphogenesis and subsequently, may expedite research in the diagnosis of osteoarthritis or the use of knockout models.We applied atomic force microscopy (AFM) imaging and indentation type (IT) AFM using murine cartilage sections at different developmental stages to investigate GP unique matrix architecture and cellular arrangement as well as the ECM within different AC zones.Within the AC we detected an increasing stiffness from the outermost layer down to the cartilage/bone interface. Furthermore, mechanical differences among young and aged AC's have been observed making AFM a reliable tool to gain information on native cartilage to form a basis to understand the onset and progression of degenerative disease.Furthermore, in the GP we observed a progressive chondrocyte flattening and arrangement into columns with a simultaneous increase in collagen density, fibril orientation and ECM stiffness. IT-AFM measurements showed a tendency to become bimodal with progressive cartilage maturation reflecting the structural changes of the collagen network of the ECM. Although these properties varied comparing different types of matrix (pericellular/interterritorial) the tendency of increasing fibril density and orientation along the proximodistal axis occurred in context with an increasing stiffness showing the strong connection between structural and mechanical properties.