Biochemical/immunochemical biomarkers of osteoarthritis: utility for prediction of incident or progressive osteoarthritis☆
Section snippets
Type II collagen
Hyaline cartilages, which include articular cartilage, have an extensive extracellular matrix that is secreted and maintained by chondrocytes. In the adult the matrix can constitute as much as 95% of the total volume of the tissue. This matrix endows cartilage with its reversible deformability and ability to dissipate load [2]. The principal structural component of cartilage is its extensive network of collagen molecules, which are arranged in fibrils, giving cartilage its tensile properties.
Issues confounding the use of biomarkers
In establishing assays for biomarkers it is important that the biomarker represents a defined product of a molecular event such as the synthesis or degradation of a matrix molecule or a combination of both (“turnover”). It is essential that researchers perform basic studies of molecular processes in tissues to understand the changes that occur in OA. By doing so researchers should be able to develop new biomarker assays more effectively and interpret the results obtained from these assays more
Preclinical studies
With the challenges in detecting early-onset human OA it is important to determine whether or not this event can be identified by biomarkers. By first using experimental animal models of OA, a more thorough assessment of the relationship of the development of tissue pathology to changes in biomarkers can be obtained. Experimentally-induced OA affords the advantage of allowing researchers to know precisely when the pathology was induced. Transection of the anterior cruciate ligament (ACL) in
Summary
In this brief review the authors endeavored to show how methods developed for molecular studies of the development, onset, and progression of OA have been used to develop biomarker assays that might be of use in the detection of incident OA and in progression of established OA (Fig. 2). These assays involve analyses of specific molecular products in body fluids that result from the cleavage and synthesis of molecules in specific skeletal tissues and from inflammatory processes associated with
Acknowledgements
The author thanks Dorothy Redhead and Guylaine Bedard who assisted in the preparation of this manuscript.
References (65)
- et al.
Analysis of collagenase-cleavage of type II collagen using a neoepitope ELISA
J Immunol Methods
(2001) - et al.
Collagen type II c-telopeptide fragments as an index of cartilage degradation
Bone
(2001) - et al.
Serum levels of cartilage oligomeric protein (COMP) correlate with radiographic progression of knee osteoarthritis
Osteoarthritis Cartilage
(2002) - et al.
C-reactive protein as a biomarker of emergent osteoarthritis
Osteoarthritis Cartilage
(2002) - et al.
Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis
Osteoarthritis Cartilage
(2001) - et al.
Serum cartilage oligomeric matrix protein and clinical signs and symptoms of potential pre-radiographic hip and knee pathology
Osteoarthritis Cartilage
(2002) - et al.
Elevation of a collagenase generated type II collagen neoepitope and a proteoglycan epitope in synovial fluid following induction of joint instability in the dog
Osteoarthritis Cartilage
(2002) - et al.
An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline
Osteoarthritis Cartilage
(2000) - et al.
Tissue inhibitor of metalloprotease-1 (TIMP-1) serum level may predict progression of hip osteoarthritis
Osteoarthritis Cartilage
(2001) - et al.
Gd-DTPA2− as a measure of cartilage degradation [erratum appears in Magn Reson Med 1996;36:964]
Magn Reson Med
(1996)
Cartilage in health and disease
Etiopathogenesis of osteoarthritis
A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine
J Bone Min Res
The association between cartilage activity measured in serum and progression of knee osteoarthritis in patients with and without evidence of generalized disease
Arthritis Rheum
Molecular basis and clinical use of biochemical markers of bone, cartilage, and synovium in joint diseases
Arthritis Rheum
Defining and validating the clinical role of molecular markers in osteoarthritis
Using molecular markers to monitor osteoarthritis
Skeletal and inflammation markers in aging and osteoarthritis. Implications for early diagnosis and monitoring of the effects of therapy
NIH white paper: biomarkers, the osteoarthritis initiative. National Institutes of Health, NIAMS News and Events
Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage
J Clin Invest
Collagenase-mediated cleavage of type II collagen is selectively enhanced in osteoarthritis cartilage and can be arrested with a synthetic inhibitor which spares collagenase-1 (MMP-1)
Arthritis Rheum
The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis
Arthritis Rheum
Increased damage to type II collagen in osteoarthritic cartilage detected by a new immunoassay
J Clin Invest
Sites of collagenase cleavage and denaturation of type II collagen in articular cartilage in ageing and osteoarthritis and their relationship to the distribution of the collagenases MMP-1 and MMP-13
Arthritis Rheum
The comparative degradation of type IX and type II collagens and proteoglycan in articular cartilage in early experimental inflammatory arthritis
Arthritis Rheum
Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis
J Exp Med
Type II collagen c-telopeptide 2B4 epitope is a marker for cartilage degradation in familial osteoarthritis [abstract]
Arthritis Rheum
The release of cross-linked peptides from type II collagen into joint fluid and serum is increased in osteoarthritis and after joint injury [abstract]
Trans Orthop Res Soc
Cross sectional evaluation of biochemical markers of bone, cartilage and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage
Ann Rheum Dis
Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage
Arthritis Rheum
Biochemical markers of bone turnover
Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis
Arthritis Rheum
Cited by (80)
Chondroprotective action of glucosamine, a chitosan monomer, on the joint health of athletes
2019, International Journal of Biological MacromoleculesCitation Excerpt :Interestingly, sports-related mechanical loading on the joints also affects the turnover rate of cartilage, and these changes can be detected by using biomarkers [1–4]. Type II collagen is one of the major components of cartilage [12], and the fragments of type II collagen are utilized as biomarkers for cartilage metabolism. A C-terminal telopeptide (CTX-II) and a neo-epitope (C2C) are cleaved during degradation of type II collagen [13,14](Fig. 2); thus, both CTX-II and C2C are used as markers for type II collagen degradation.
Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β
2015, International ImmunopharmacologyCitation Excerpt :Numerous studies have demonstrated that MMPs are most frequently implicated in the destruction of articular cartilage in arthritic diseases. MMP-3 may indirectly contribute to the breakdown of type II collagen by activating other MMPs such as MMP-9 and MMP-13 [31,32]. MMP-9 plays an important role in angiogenesis in RA and OA [33], and MMP-13 is the most common downstream target that is up-regulated or inappropriately activated at different times during the OA disease process by stress or pro-inflammatory-like signals [34,35].
Association between serum levels of aggrecan ARGS and NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients
2012, Revue du Rhumatisme (Edition Francaise)CC chemokines and receptors in osteoarthritis: new insights and potential targets
2023, Arthritis Research and Therapy
- ☆
The author's research is funded by the Shriners Hospitals for Children, the Canadian Institutes of Health Research, the National Institute of Aging, the National Institutes of Health, and the Canadian Arthritis Network.