## 2 Anatomy of Articular Cartilage
### Metabolism  
The matrix of the adult articular cartilage is separated by the subchondral plate from the subchondral vascular spaces. Diffusion from synovial fluid affects AC nutrition. The cartilage matrix restricts materials in terms of size, molecular configuration and charge [2]. The average pore size in the ECM is approximately 6.0 nm [129]. Due to the lack of direct nutrient supply from the lymphatic or blood vessels, mainly anaerobic metabolism affects the chondrocytes.  
The development, maintenance as well as repair of the ECM is the task of chondrocytes via a group of degrading enzymes. The role of chondrocytes is to synthesise matrix components, proteins and glycosaminoglycan side chains. Factors surrounding chondrocytes in the mechanical and chemical environment affect their metabolic activity. Pro-inflammatory cytokines are characterised by anabolic and catabolic effects that function in the synthesis and degradation of matrix macromolecules [130].  
Chondrocytes influence the synthesis, maintenance and secretion of proteoglycans into the ECM. A number of growth factors and regulatory peptides are involved in the regulation of proteoglycan metabolism, including transforming growth factor-\(\beta\), interleukin-1 and tumour necrosis factor-\(\alpha\). However, further studies are needed to expand the knowledge of the molecular mechanism by which these peptides and growth factors affect proteoglycan metabolism.  
The ECM surrounds chondrocytes, thereby protecting them from harmful biomechanical forces. ECM metabolic homeostasis contributes to balancing the degradation of macromolecules with their replacement by newly synthesised products. It is estimated that proteoglycan turnover can last up to 25 years, while the half-life of collagen is estimated to be from several decades to 400 years [94; 131].  
The main proteinases involved in cartilage turnover are metalloproteinases (gelatinase, stromelysin and collagenase) as well as cathepsins (B and D). The function of gelatinase is to degrade denatured collagen types II and IV, and also has significant activity against collagen types V, VII, X, XI, elastin and fibronectin [132; 133]. Stromelysin is responsible for the degradation of the aggrecan protein core. In turn, the function of collagenase is to degrade spiral native collagen fibres in one place [2]. Metalloproteinases are secreted as latent proenzymes that require extracellular activation. Cathepsins are active in the process of aggrecan degradation.  
Movement and joint loading are necessary to maintain both the proper structure and function of the AC. A lack of physical activity affects cartilage degradation [41]. Dynamic loads and systematic movement are extremely important to ensure proper AC metabolism. Changes in cartilage metabolism may occur as a result of diseases, such as osteoarthritis, which is caused by a physiological imbalance between synthesis by chondrocytes and degradation [134].  
Understanding the unique physiological properties of AC is intrinsically linked to its structure, more specifically its zonation and regional organisation, cellular composition and ECM composition. This is the key knowledge required to further analyse the biomechanical parameters of AC, which will be discussed in detail in the next section.