## 2 Anatomy of Articular Cartilage
### Chondrocytes
Osteoarthritis has been observed to be associated with a higher expression of Runx2 in chondrocytes, compared to normal chondrocytes [72]. In contrast, a decrease in this factor contributes to slowing the progression of OA. In conclusion, Runx2 can be described as an important factor in chondrocyte maturation, and it is also involved in the pathogenesis of OA. Mature chondrocytes are responsible for the production of collagen types II, IX and XI (COL2, COL9, COL11), structural proteins and ACAN [73]. The task of chondrocytes with a natural and intact phenotype is to synthesise lubricin, proteoglycan-4 (PRG4), and a glycoprotein [57]. Chondrocytes have an extremely important lubricating function, thus reducing friction between adjacent cartilage surfaces. The inhibitory effect on inflammatory cytokines and their activation of synovial membrane fibroblast proliferation is demonstrated by PRG4 [74]. Integrins have an important function in cell adhesion and cell-to-cell and ECM interactions [57]. Integrins can be characterised as transmembrane receptors whose function is to recognise specific ECM molecules [2; 75; 76]. Chondrocytes are characterised by the expression of integrins \(\alpha\)1\(\beta\)1, \(\alpha\)3\(\beta\)1, \(\alpha\)5\(\beta\)1, \(\alpha\)0\(\beta\)1, \(\alpha\)V\(\beta\)1, \(\alpha\)V\(\beta\)3 and \(\alpha\)V\(\beta\)5 [77; 78]. An important integrin whose role is to bind COL2 in cartilage tissue is integrin \(\alpha\)10\(\beta\)1. It also acts as a marker to determine the phenotype of chondrocytes. Integrin \(\alpha\)10\(\beta\)1 is a component of the cell-matrix interaction required for cartilage development and MSC chondrogenesis [77; 79]. Chondrocytes express the types of integrins that bind to ECM molecules [80]. The hyaluron receptor CD44 is an isotopic membrane receptor of chondrocytes [81]. The binding of chondrocytes and HA affects the homeostasis of the cartilage environment, and if this binding is blocked, the ECM is damaged and degraded [80; 82]. Cell metabolism is also regulated by the release of soluble factors [57]. The transforming growth factor-beta (TGF-\(\beta\)) superfamily plays a key role in pathological and physiological phenomena by influencing tissue cell growth and differentiation, and adhesion [83]. This group of activins includes more than 30 proteins and bone morphogenetic proteins (BMPs) [84]. They take part in the maintenance of homeostasis, immune events and embryogenesis [85; 86]. TGF-\(\beta\) is involved in the formation of cartilage, as well as bone tissue [87]. TGF-1 is one of the most extensively studied growth factors [88]. TGF-2 has also been the subject of research into disorders and the treatment of cartilage defects [89]. It is involved in the activation of mitogen-activated protein kinase (MAPK) in chondrocytes [50]. BMPs belong to the TGF-\(\beta\) family, showing stimulatory effects in the process of chondrogenesis. Their role is also to support the condensation step at the onset of chondrogenesis. In addition, BMPs affect the expression of COL2 and Sox9 [58]. Chondrocytes can vary in number, shape and size depending on the zones in which they are located. In the superficial zone, they are smaller, denser, and their shape is flatter compared to the chondrocytes found deeper in the matrix. Chondrocytes do not normally form intercellular contacts for intercellular communication or direct signal transmission. Their response is related to factors such as growth factors, piezoelectric forces, mechanical loads, and hydrostatic pressure [90]. Due to the limited replication potential of these cells, the intrinsic healing capacity of cartilage is limited.