“…Some of the major extracellular (ECM) constituents of the tissues in the joint are type I, II, and III collagen (37) that are degraded in the rheumatic pathologies, resulting in the release of protein fingerprints. Matrix metalloproteinase (MMP)-mediated degradation of these collagens results in the generation of the specific biomarkers C1M, C2M, and C3M, respectively (38,39), while other protein fingerprints, such as C-telopeptide of type I collagen (CTX-I), C-terminal crosslinking telopeptide of type I collagen generated by MMPs (ICTP), C-telopeptide of type II collagen (CTX-II), C2C, NITEGE (aggrecan), FFGV (aggrecan), C4M (type IV collagen), C5M (type V collagen), or C6M (type VI collagen), represent other distinct enzymatic processing of either the same or other ECM molecules (1,36). Measuring different degradation products of a protein may inform different and opposing metabolic mechanisms, exemplified by the characterization of type I collagen (Figure 3).…”