## 4 Articular Synovial Parameters
### Synovial Membrane  
The synovial membrane is a highly specialised mesenchymal tissue whose functions are to provide the joints with adequate lubrication and to supply nutrients to the AC [264; 265]. It also provides a mechanical barrier that separates the joint cavity from the blood and lymphatic vessels, and is involved in the production and resorption of SF [250]. The structure of the SM consists of two layers: the intima inner layer, and the subintima inner layer [266]. The intima inner layer consists of one or two sheets of macrophages or synovocytes, which are similar to fibroblasts. The subintima inner layer consists of two or three layers of synovocytes lying over loose connective tissue containing fibroblasts that secrete collagen and other extracellular matrix proteins [266]. The cells inside the synovial membrane are responsible for the secretion of synovial fluid, providing lubrication to the AC, nutrition and also the activity of the chondrocytes. Type A and B synovocytes are part of the synovial intima [237]. Type A synovocytes are the tissue macrophages of the SM, located around the upper lining of the synovial membrane [237; 264; 266]. Their function is to absorb and degrade extracellular components, as well as joint cavity debris, antigens and microorganisms. These cells have the ability to proliferate under inflammatory conditions. SM macrophages contribute to cartilage destruction under pathological conditions. Chronic production of pro-inflammatory cytokines and osteophyte formation due to the release of transforming growth factor-beta (TGF-\(\beta\)), as well as bone morphogenetic protein BMP-2 and BMP-4, are responsible for this condition [267; 268]. Type B synovocytes, also known as synovial membrane fibroblasts, are located below the type A synovocytes, on the submental layer, forming the surface of the synovial membrane [269]. Their function is to produce components such as proteoglycans, collagen types III, IV, V, VI, fibronectin, glycosaminoglycans, entactin and laminin [250; 269]. In addition, they are responsible for the production of lubricin [237; 270]. Characteristic of type B synovocytes are the dendritic cytoplasmic protrusions observed in SM [269; 271]. These cells usually have one or more protrusions that are directed towards the surface of the synovial membrane, either in different directions or parallel to the surface of the membrane, and that overlap to form a plexus [271]. With their cytoplasmic protrusions, type B synovocytes reach deep into the joint cavity to analyse and control the composition of the SF [250]. Despite the leaky structure of the synovial membrane containing 1-\(\upmu\)m-diameter pores between synoviocytes, it ensures that proper quality SF is maintained [264]. The structure of the intercellular matrix is mainly responsible for the resistance of the SM against water leakage from the joint cavity [272]. This process depends on the concentration of proteoglycans, glycosaminoglycans and glycoproteins between collagen fibrils due to the migration of SF through thin intermolecular spaces [264; 273]. SM is also responsible for limiting the efflux of HA from the SF, so that a high concentration of this component is maintained in the joint cavity [272]. In the process of extruding fluid into the joint, HA accumulates on the surface of the synovial membrane, thus creating a buffer layer [274]. When the molecular weight of the HA or its concentration is reduced, there is an increased discharge of HA from the joint cavity [272]. Patients affected by OA experience SM proliferation, resulting in thickening of the SM and remodelling of the tissue architecture [275]. Osteoarthritis is considered a degenerative disease, but inflammatory processes have been shown to be significantly involved at the level of the synovial membrane [237]. Activation of A and B synoviocytes occurs, resulting in increased release of growth factors and inflammatory mediators, which include TNF-\(\alpha\), IL-1\(\beta\) and prostaglandam [237].