A multiparameter approach to monitor disease activity in collagen-induced arthritis

Abstract

IntroductionDisease severity in collagen-induced arthritis (CIA) is commonly assessed by clinical scoring of paw swelling and histological examination of joints. Although this is an accurate approach, it is also labour-intensive and the application of less invasive and less time-consuming methods is of great interest. However, it is still unclear which of these methods represents the most discriminating measure of disease activity.MethodsWe undertook a comparative analysis in which different measurements of inflammation and tissue damage in CIA were studied on an individual mouse level. We compared the current gold standard methods - clinical scoring and histological examination - with alternative methods based on scoring of X-ray or micro-computed tomography (CT) images and investigated the significance of systemically expressed proteins, involved in CIA pathogenesis, that have potential as biomarkers.ResultsLinear regression analysis revealed a marked association of serum matrix metalloproteinase (MMP)-3 levels with all features of CIA including inflammation, cartilage destruction and bone erosions. This association was improved by combined detection of MMP-3 and anti-collagen IgG2a antibody concentrations. In addition, combined analysis of both X-ray and micro-CT images was found to be predictive for cartilage and bone damage. Most remarkably, validation analysis using an independent data set proved that variations in disease severity, induced by different therapies, could be accurately represented by predicted values based on the proposed parameters.ConclusionsOur analyses revealed that clinical scoring, combined with serum MMP-3, anti-collagen IgG2a measurement and scoring of X-ray and micro-CT images, yields a comprehensive insight into the different aspects of disease activity in CIA.

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

“…MicroCT has become an important tool for the analysis of bone morphology and has previously been used in the CIA murine model (20). MicroCT analysis of the long bones from ox40l −/− mice revealed basal bone turnover defects (Fig.…”

Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis

“…2B). It has been reported that serum matrix metalloproteinase (MMP)-3 is a good indicator in the inflammatory aspect and cartilage damage of CIA (29). Serum levels of MMP-3 are elevated in RA, providing a useful marker of synovial inflammatory activity (30).…”

Contrast-enhanced nanofocus computed tomography images the cartilage subtissue architecture in three dimensions

“…Micro-CT has been reported frequently for imaging and assessing ex vivo the effect of different types of arthritis on the bone structure (Buttgereit et al, 2009;Herrak et al, 2004), surface roughness (Seeuws et al, 2010) and density (Healy et al, 2006). Although this technique allows investigation of the effect of arthritis on the underlying bone, nothing can be concluded concerning cartilage structure and functionality.…”