Table A2.
List of Biomarker Abbreviations With a Summary of Biomarker Function
| Abbreviation | Full Name | Basic Function | Included Study Reporting on Biomarker |
|---|---|---|---|
| Aggrecan | Aggrecan | Major proteoglycan in articular cartilage 28 | Pietrosimone 54 |
| ALT | Alanine transaminase (also known as alanine aminotransferase) | Enzyme found mostly in hepatocytes that catalyzes the reversible interconversion of l-alanine and 2-oxoglutalate to pyruvate and l-glutamate 41 ; has also been found to be elevated in skeletal muscle diseases 49 | Kodama 32 |
| AST | Aspartate transaminase (also known as aspartate aminotransferase) | Enzyme found mostly in hepatocytes; catalyzes the transamination reaction between l-aspartate and 2-oxoglutarate into oxaloacetate and l-glutamate 31 ; also found to be elevated in skeletal muscle diseases 49 | Kodama 32 |
| Bilirubin + biliverdin | Bilirubin and biliverdin | By-product of heme catabolism and is subsequently reduced to bilirubin 47 | Amano 3 |
| BMP-2 | Bone morphogenic protein 2 | Role in signaling osteoblast proliferation and differentiation 6 | Zysk 69 |
| C1,2C | Collagen type 1 and 2 cleavage product | By-product of type 1 and 2 collagen cleavage by collagenases 61 | Tourville 63 |
| C2C | Collagen type 2 cleavage product | By-product of cleavage of type 2 collagen cleavage by collagenases 61 | Lisee, 40 Pietrosimone,53,54 Sobue, 56 Tourville 63 |
| C2C/CPII | Collagen type 2 cleavage product/procollagen 2 carboxypeptide | Ratio of type 2 collagen degradation relative to synthesis 40 | Lisee, 40 Pietrosimone 53 |
| C2C/KS | Collagen type 2 cleavage product/keratan sulfate | Ratio of C2C/KS in synovial fluid that may offer greater ability to identify early, pre-radiographic high-grade cartilage damage better than either biomarker individually56,68 | Sobue 56 |
| C4S | Chondroitin-4-sulfate | In osteoarthritic cartilage, C6S is replaced by C4S 48 | Sobue 56 |
| C6S | Chondroitin-6-sulfate | Major glycosaminoglycan found in articular cartilage 48 | Sobue 56 |
| C6S/C4S | Chondroitin-6-sulfate/chondroitin-4-sulfate | Ratio of C6S to C4S, considered to be a marker of osteoarthritis progression 48 | Sobue 56 |
| COMP | Cartilage oligomeric matrix protein | Extracellular matrix protein that binds to aggrecan; considered to be a biomarker of matrix degeneration 40 | Latterman, 36 Lisee 40 |
| CPII | Procollagen 2 C-propeptide | Marker of type 2 collagen synthesis 61 | Amano, 3 Tourville 63 |
| CRP | C-reactive protein | Acute inflammatory protein synthesized primarily in the liver 57 | Kodama 32 |
| CTX-II | C-terminal cross-linked telopeptide of type 2 collagen | By-product of type 2 collagen and articular cartilage degradation 7 | Chmielewski, 7 Latterman, 36 Tourville 63 |
| FGF-2 (bFGF) | Fibroblast growth factor 2 (also known as basic fibroblast growth factor) | Growth factor promoting chondrogenesis, angiogenesis, wound healing, and granulation tissue formation; excess may contribute to onset or progression of osteoarthritis4,24 | Avila, 4 Markus 44 |
| IFN-γ | Interferon gamma | Pro-inflammatory cytokine that has been used as a marker of cartilage degeneration3,62 | Amano, 3 Inoue 25 |
| IL-1 | Interleukin 1 | Refers to IL-1a and IL-1b, 2 cytokines that play a major role in inflammation 26 | Gupta 19 |
| IL-1a | Interleukin 1 alpha | Pro-inflammatory cytokine produced by macrophages and epithelial cells 3 | Amano, 3 Latterman 36 |
| IL-1b | Interleukin 1 beta | Pro-inflammatory cytokine produced by macrophages and epithelial cells 3 | Amano, 3 Inoue, 25 Latterman, 36 Sullivan, 60 Zysk 69 |
| IL-1Ra | Interleukin 1 receptor antagonist | Anti-inflammatory cytokine that inhibits the effect of IL-1b4,26 | Amano, 3 Avila, 4 Latterman, 36 Markus 44 |
| IL-2 | Interleukin 2 | Cytokine produced by activated T cells with a role in mediating the immune system by promoting growth and differentiation of T cells, T-helper cells, and NK cells 23 | Amano, 3 Inoue 25 |
| IL-4 | Interleukin 4 | Cytokine produced by Th2 cells and mast cells; involved in B-cell activation, IgE switch, and suppression of Th1 cells 26 | Amano 3 |
| IL-6 | Interleukin 6 | Cytokine secreted by T cells, macrophages, and endothelial cells during infection or trauma, stimulating IL-10 and IL-1Ra to act as a negative feedback mechanism to inflammation4,17 | Amano, 3 Avila, 4 Evans-Pickett, 15 Gupta, 19 Inoue, 25 Markus, 44 Pietrosimone, 53 Sobue, 56 Sullivan, 60 Zysk 69 |
| IL-8 | Interleukin 8 | Cytokine produced by monocytes that attracts neutrophils, basophils, and T cells 23 | Amano, 3 Inoue 25 |
| IL-10 | Interleukin 10 | Anti-inflammatory cytokine produced by Th2 cells and macrophages that inhibits Th1 cells, increases MHC expression on B cells, and stimulates mast cell growth 23 | Amano, 3 Inoue 25 |
| IL-12p70 | Interleukin 12p70 | Active form of cytokine IL-12 produced by B cells and macrophages that induces NK-cell activation and Th1-cell differentiation 23 | Amano 3 |
| IL-13 | Interleukin 13 | Anti-inflammatory cytokine produced by T cells; acts to promote B-cell growth/differentiation, inhibit macrophage cytokine production, and inhibit Th1 cells 23 | Amano 3 |
| KS | Keratan sulfate | A glycosaminoglycan that is one of the constituent proteins of aggrecan when attached to a core protein 56 ; levels are decreased in cartilage degradation 68 | Sobue 56 |
| MCP-1 (CCL2) | Monocyte chemotactic protein 1 (also known as chemokine ligand 2) | Chemokine that recruits monocytes, memory T cells, and dendritic cells to inflammatory sites4,12 | Avila, 4 Lisee, 40 Markus 44 |
| MIP-1B | Macrophage inflammatory protein 1B | Chemokine produced by neutrophils that activates granulocytes; recruits neutrophiles/monocytes/macrophages/immature dendritic cells/Th1 cells to inflammatory sites 4 | Avila, 4 Markus 44 |
| MMP-1 | Matrix metalloproteinase 1 | Metalloproteinase that degrades type 1, 2, 3, 7, 8, and 10 collagen and gelatin, aggrecan, and proteoglycan link proteins 12 | Amano, 3 Latterman 36 |
| MMP-3 | Matrix metalloproteinase 3 | Metalloproteinase that degrades type 2, 4, 9, 10, and 11 collagen and proteoglycans, fibronectin, laminin, and elastin; can activate other MMPs4,14 | Amano, 3 Avila, 4 Evans-Pickett, 15 Latterman, 36 Lisee, 40 Markus, 44 Pietrosimone 53 |
| MMP-9 | Matrix metalloproteinase 9 | Metalloproteinase that degrades type 4, 5, 7, 10, and 14 collagen and gelatin, aggrecan, elastin, fibronectin, laminin, and proteoglycan link protein 11 | Amano, 3 Latterman 36 |
| NO | Nitric oxide | A free radical shown to have a role on potentiating cytokine and inflammation-induced bone resorption65,69 | Zysk 69 |
| NTX-1 | N-terminal telopeptide of type 1 collagen | Marker of breakdown of type 1 collagen and indicator of bone turnover3,36 | Latterman, 36 Amano 3 |
| RANTES (CCL5) | Regulated on activation, normal T cell expressed and presumably secreted (also known as chemokine ligand 5) | Chemokine that recruits leukocytes to the site of inflammation and activates natural killer cells4,55 | Avila, 4 Markus 44 |
| sGAG | Sulfated glycosaminoglycan | A class of long, linear polysaccharides that includes the chondroitin sulfate (eg, C4S, C6S) and keratan sulfate (KS) groups 64 | Amano, 3 Latterman 36 |
| TIMP-1 | Tissue inhibitor of metalloproteinases 1 | Protein that inhibits MMPs; promotes cell growth of chondrocytes and has chondroprotective effect4,18 | Avila, 4 Markus 44 |
| TIMP-2 | Tissue inhibitor of metalloproteinases 2 | Protein that inhibits MMPs, favoring MMP-2 46 | Markus 44 |
| TNF-α | Tumor necrosis factor alpha | Pro-inflammatory cytokine produced by macrophages1,3 | Amano, 3 Gupta, 19 Inoue, 25 Zysk 69 |
| TSG-6 | Tumor necrosis factor–stimulated gene 6 protein | Anti-inflammatory protein significantly upregulated in osteoarthritis progression 8 | Latterman 36 |
| TTT | Thymol turbidity test | A marker of inflammatory conditions such as chronic hepatitis, chronic infection, or collagen disease 32 | Kodama 32 |
| VEGF | Vascular endothelial growth factor | Growth factor that induces angiogenesis4,45 | Avila, 4 Markus 44 |