Biochemical markers analysed in the APPROACH cohort sampled from serum (S) and urine (U)
| Name | Inter- and intra-CV | Detection range | Description |
| S_C3M | <15% | 1–85 ng/mL | Matrix metalloproteinase (MMP)-mediated type III collagen degradation fragment. Type III collagen is a major collagen of connective tissues, including synovial membrane. C3M has been shown to be released from synovial membranes in the presence of proinflammatory cytokines which activate MMPs.43 |
| S_CRPM | <15% | 1–110 ng/mL | MMP-mediated C reactive protein (CRP) degradation fragment. CRP is an acute reactant elevated in chronic inflammatory diseases. CRPM is a metabolite of CRP.44 |
| S_ARGS | <15% | 0.01–0.40 pmol/mL | ADAMTS-mediated aggrecan degradation products. Aggrecan is the major proteoglycan of articular cartilage. Like MMPs, ADAMTS are expressed and activated in the presence of proinflammatory cytokines.45 |
| S_C10C | <15% | 500–7500 ng/mL | Cathepsin K-mediated type X collagen degradation fragment. Type X collagen is a minor collagen expressed by the cartilage cells called chondrocytes.46 |
| S_C2M | <15% | 0–10 ng/mL | MMP-mediated type II collagen degradation fragment. Type 2 collagen is the major fibrillar protein of cartilage and C2M is released on activation of MMPs.47 |
| S_COLL2_1 | <15% | 200–2200 nM | Type II collagen degradation fragment similar, but from a different domain compared with C2M.48 |
| S_COLL2_1NO2 | <15% | 150–6000 pg/mL | Inflammation-related (nitrated) type-II collagen degradation fragment. Nitrosylation is a post-translational modification induced by an increase in oxidative stress associated with inflammation.48 |
| S_COMP | <15% | 1–50 units/L | Cartilage oligomeric matrix protein. COMP is articular cartilage protein, which is released when cartilage is turned over.49 |
| S_CTXI | <10% | 0–3 ng/mL | Cross-linked, isomerised and cathepsin K-generated fragment of type I collagen C-terminal telopeptide. Type I collagen is the major fibrillar protein of bone and some connective tissues. Cathepsin K is mainly expressed by osteoclast, making CTX-I a marker of bone resorption.50 |
| S_HA | <15% | 10–800 ng/mL | Hyaluronic acid is a glycosaminoglycan distributed widely across connective, epithelial and neural tissues, including articular cartilage. It is released as part of tissue remodelling and turnover induced by, for example, inflammation.50 |
| S_hsCRP | <10% | 0–60 mg/L | High-sensitive C reactive protein (hsCRP) is an acute reactant elevated in chronic inflammatory diseases and used as a diagnostic marker in different rheumatic diseases.51 |
| S_PRO_C2 | <10% | 5–1000 ng/mL | Type IIB collagen propeptide (synthesis). When new type II collagen is expressed by cartilage cells, PRO-C2 is released and is a reflection of cartilage formation.12 |
| S_NMID | <10% | 1–180 ng/mL | Bone gamma-carboxyglutamic acid-containing protein.52 |
| S_RE_C1M | <15% | 10–500 ng/mL | MMP-mediated type I collagen degradation. See S_C3M and S_CTX-I.53 |
| U_CTXI_ALPHA | <15% | 0–10 μg/mmol | Cathepsin K-generated fragment of type I collagen C-terminal telopeptide (corrected for creatinine) is a non-isomerised version of S_CTX-I and therefore believed to reflect degradation of young bone in contrast to the isomerised which measures old bone.54 |
| U-CTXII | <15% | 10–2500 ng/mmol | MMP- and cathepsin K-mediated type II collagen degradation fragment (corrected for creatinine). See CTX-I and C2M as well.50 |
Coefficient of variation (CV) and detection range are shown; for further assay validation, see references.