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Synovial Fluid

TNF-α // Tumor Necrosis Factor alpha

Tumor Necrosis Factor α (TNFα) is a pleiotropic cytokine mainly produced by monocytes and macrophages. It was initially found to have a cytotoxic effect on tumor cells and took its name from this. This cytokine exists as a soluble and mature form and as an unprocessed membrane bound form. The soluble form can form an active homo-dimer and an homo-trimer (Barbara et al., 1996; Semenzato, 1990). TNF is shed from the membrane by the metalloprotease ADAM17 (or TACE) and released on the circulation were it can have its central role in the inflammatory response (Gooz, 2010; Old, 1985)

TIMP-1 // Tissue Inhibitor of Metalloproteinase 1

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). Tissue Inhibitor of Metalloproteinase family comprises 4 members. They are two-domain proteins with a N-Terminal domain of approximately 125 residues and a C terminal domain of about 65 residues (Brew et al., 2000).

PGE2 // Prostaglandin E2

Prostaglandin E2, derived from arachinoic acid, is implicated in a wide variety of process: paracrine mediator of the Luteinizing Hormone surge as well as stimulating inflammation in osteoarthritis and rheumatoid arthritis (Duffy, 2015; Park et al., 2006). In osteoarthritis, its synthesis is promoted indirectly (through Cyclooxygenase-2 upregulation) by pro-inflammatory cytokines such as IL-1β and TNF-α (Martel-Pelletier et al., 2003).

Bioclinica Lab employs a competitive immunoassay for measurement of PGE2 in synovial fluid.

MMP-13 // Pro-Matrix Metalloproteinase 13

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). MMP-13 is also called collagenase 3 and cleaves the interstitial collagens types I, II and III with a high potency against collagen of type II (the major component of cartilage)(Leeman et al., 2002).

MMP-8 // Total Matrix Metalloproteinase 8

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). MMP-8 is also known as collagenase-2 or neutrophil collagenase and is implicated in the degradation of a wide range of substrates: type I, II and III collagens, proteoglycans, fibronectin, fibrinogen, angiotensin I, substance P, Angiotensin, CXCL10 and many others (Lenglet et al., 2013; Van Lint and Libert, 2006).

MMP-3 // Active and Pro-Matrix Metalloproteinase 3

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). Matrix metalloproteinase 3 (MMP-3, also known as stromelysin-1), secreted by chondrocytes and synovial cells, activates other proteases and has a broad substrate specificity for degrading extracellular matrix components (fibronectin, laminin, elastin, collagen IV, and proteoglycans)(Kim and Hwang, 2011; Murphy et al., 1991).

IL-6 // Interleukin 6

Interleukin 6 (IL-6) was initially identified as a differentiation factor for B-cells and was then named: B-cell stimulatory factor 2 (Naka et al., 2002). IL-6 is a pleiotropic cytokine produced by different types of cells (T cells, B cells, monocytes, fibroblasts, keratinocytes, endothelial cells, mesangial cells and some tumor cells). This cytokine has also a wide range of effect on different target through trans- or classical signaling with the IL-6R system (Calabrese and Rose-John, 2014).

CS846 // Chondroitin Sulfate 846 Epitope

Chondroitin Sulfate epitope 846 (CS846) is an epitope present in newly synthetized agreccan molecules. CS846 is increased in joints and synovial fluid of patients with rheumatoid arthritis or osteoarthritis (Lohmander et al., 1999; Rizkalla et al., 1992; Verstappen et al., 2006). These increased levels in serum may reflect pathological increase in turnover of newly formed matrix, something that is not seen in healthy adult cartilage. To date, serum CS846 is also one of the 12 best-qualified biochemical markers that have shown associations with osteoarthritis (Hunter et al., 2014).

COMP // Cartilage Oligomeric Matrix Protein

Cartilage oligomeric matrix protein (COMP) is also called thrombospondin-5 (TSP-5). COMP possess a RGD motif which allow interaction with integrins (Tan et al., 2009). COMP can bind to chondrocytes (the only cell type found in cartilage) and promote early stages of chondrogenic differentiation of mesenchymal stem cells, in association with bone morphogenic protein-2 (BMP-2)(Chen et al., 2005). Serum COMP is elevated in patients with diagnosed OA (level of evidence grade C) (Hoch et al., 2011).

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