Value of Biomarkers in Osteoarthritis
Value of Biomarkers in Osteoarthritis
The best candidates for biomarkers in osteoarthritis are most likely to be structural molecules or fragments linked to cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. They may represent tissue degradation or tissue synthesis and may be measured in synovial fluid, blood or urine. Box 1 and figure 1 outline a selection of the various biomarkers that are currently being tested in osteoarthritis. Figure 1 highlights the different compartments of the joint and potential biomarkers, all of which require careful investigation. The cartilage, bone and synovial tissues all have different potential biomarkers for investigation, each of which has their own strengths and weaknesses. Discussion of each of the individual markers can be found elsewhere in the literature. Many are associated with the metabolism of collagen in cartilage (type II collagen) or subchondral bone (type I collagen) or the metabolism of aggrecan in cartilage. Together, type II collagen and aggrecan constitute the most abundant proteins in the cartilage matrix, making them promising targets for research. In addition, there are biomarkers related to a range of non-collagenous proteins that have a role in other metabolic pathways in the joint, including glycoproteins, proteoglycans, metalloproteinases and advanced glycation endproducts, as well as hyaluronan, which is a constituent of both cartilage and synovium. Finally, there are a number of biomarkers associated with other processes, such as inflammation or fibrosis.
(Enlarge Image)
Figure 1.
Sources of possible biomarkers in osteoarthritis. C2C, cleavage of type II collagen; C2M, collagen type II-specific neoepitope; C3M, collagen type III-specific neoepitope; Coll 2-1, 9-amino acid peptide of type II collagen (nitrated form Coll 2-1 NO2); COMP, cartilage oligomeric protein; CPII, type II collagen propeptide; CRP, C reactive protein; CTX, C-terminal telopeptide of collagen; DKK, wnt inhibitor; FSTL-1, follistatin-like protein 1; ICTP, type I collagen-derived cross-linked carboxy-terminal telopeptide; IL, interleukin; MMP, matrix metalloproteinase; NTX, N-terminal telopeptide of collagen OPG, osteoprotegerin; PIIANP, N-propeptide IIA of type II collagen; PIIBNP, N-propeptide IIB of type II collagen; PIICP, C-propeptide of collagen type II; PINP, N-propeptide of type I collagen; PIINP, N-propeptide of type II collagen; RANK-L, receptor activator of nuclear factor κB ligand; RAGE, receptor for advanced glycation endproducts; TNF, tumour necrosis factor.
Candidate Biomarkers in Osteoarthritis
The best candidates for biomarkers in osteoarthritis are most likely to be structural molecules or fragments linked to cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. They may represent tissue degradation or tissue synthesis and may be measured in synovial fluid, blood or urine. Box 1 and figure 1 outline a selection of the various biomarkers that are currently being tested in osteoarthritis. Figure 1 highlights the different compartments of the joint and potential biomarkers, all of which require careful investigation. The cartilage, bone and synovial tissues all have different potential biomarkers for investigation, each of which has their own strengths and weaknesses. Discussion of each of the individual markers can be found elsewhere in the literature. Many are associated with the metabolism of collagen in cartilage (type II collagen) or subchondral bone (type I collagen) or the metabolism of aggrecan in cartilage. Together, type II collagen and aggrecan constitute the most abundant proteins in the cartilage matrix, making them promising targets for research. In addition, there are biomarkers related to a range of non-collagenous proteins that have a role in other metabolic pathways in the joint, including glycoproteins, proteoglycans, metalloproteinases and advanced glycation endproducts, as well as hyaluronan, which is a constituent of both cartilage and synovium. Finally, there are a number of biomarkers associated with other processes, such as inflammation or fibrosis.
(Enlarge Image)
Figure 1.
Sources of possible biomarkers in osteoarthritis. C2C, cleavage of type II collagen; C2M, collagen type II-specific neoepitope; C3M, collagen type III-specific neoepitope; Coll 2-1, 9-amino acid peptide of type II collagen (nitrated form Coll 2-1 NO2); COMP, cartilage oligomeric protein; CPII, type II collagen propeptide; CRP, C reactive protein; CTX, C-terminal telopeptide of collagen; DKK, wnt inhibitor; FSTL-1, follistatin-like protein 1; ICTP, type I collagen-derived cross-linked carboxy-terminal telopeptide; IL, interleukin; MMP, matrix metalloproteinase; NTX, N-terminal telopeptide of collagen OPG, osteoprotegerin; PIIANP, N-propeptide IIA of type II collagen; PIIBNP, N-propeptide IIB of type II collagen; PIICP, C-propeptide of collagen type II; PINP, N-propeptide of type I collagen; PIINP, N-propeptide of type II collagen; RANK-L, receptor activator of nuclear factor κB ligand; RAGE, receptor for advanced glycation endproducts; TNF, tumour necrosis factor.
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