Biological markers in osteoarthritis

Abstract

Osteoarthritis (OA) is a progressive disorder characterized by destruction of articular cartilage and subchondral bone, and by synovial changes. The diagnosis of OA is generally based on clinical and radiographic changes, which occur fairly late during disease progression and have poor sensitivity for monitoring disease progression. Progression of joint damage is likely to result primarily from an imbalance between cartilage degradation and repair, so measuring markers of these processes would seem a promising approach to improve the prediction of disease progression at the individual level. Moreover, genetic markers might be useful predictors of prognosis. The lack of fully effective, chondroprotective medications has limited the use of such potential markers to monitor the effect of treatment for OA. Nevertheless, owing to their dynamic changes in response to treatment, biological markers might provide relevant information more rapidly than imaging techniques (such as radiography and MRI) can, and should contribute to our understanding of mechanisms that underlie the clinical efficacy of OA treatments. Most of the identified genes involved in OA encode signal-transduction proteins, which provide the potential for novel therapeutic approaches. In this Review, we will use the recently proposed BIPED (i.e. burden of disease, investigative, prognostic, efficacy of intervention and diagnostic) classification of OA markers to describe the potential usage of a given marker.

Cartilage degradation biomarkers predict efficacy of a novel, highly selective matrix metalloproteinase 13 inhibitor in a dog model of osteoarthritis: Confirmation by multivariate analysis that modulation of type ii collagen and aggrecan degradation peptides parallels pathologic changes

“…Full-length recombinant human proteins were used for MMPs 1, 2, 9, and 13. The catalytic domain of the protein was used for MMPs 3,7,8,10,12,14,15,16,20,24,25, and 26. PF152 potency was also evaluated using full-length bovine type II collagen by quantifying the generation of the one-quarter-length and threequarter-length fragments upon digestion with full-length human MMP-13 using sodium dodecyl sulfate-polyacrylamide gel electrophoresis.…”

“…Therefore, the identification and validation of biomarkers that predict the efficacy of potential OA drugs faster and/or with fewer patients is important for the development of DMOADs. Many biomarkers reflecting degradation of various tissues in OA joints have been described, but their predictive value as surrogates for JSN is still under investigation (8)(9)(10)(11)(12)(13)(14)(15).…”

Proteomic characterization of mouse cartilage degradation in vitro

“…A principal component of this process is the proteolytic cleavage of target macromolecules of the extracellular matrix (ECM) and the release of proteins and protein fragments from cartilage into synovial fluid. Such proteolytic products are potential biomarkers of disease activity, and their presence in vivo can be exploited for the early detection of cartilage degeneration or for monitoring the efficacy of arthritis treatments (1). The identification of biologic markers that correlate with the onset and progression of cartilage degeneration in patients with arthritis is therefore a major goal in arthritis research.…”

Biomarcadores en espondiloartropatías

“…Finalmente existe un tema de interés y son los resultados de los biomarcadores que refl ejan el recambio de cartílago, aunque estos marcadores son más utilizados en osteoartrosis, el cartílago también es un órgano blanco importante en las EAS 44 . Los biomarcadores de la síntesis y degradación de cartílago son índices potenciales que refl ejen actividad de la enfermedad.…”