Abstract

It is increasingly recognized that early detection of bone erosion plays an important role in the overall evaluation of rheumatoid arthritis and in the choice of the correct treatment approach. Since an appropriate use of imaging biomarkers in preclinical settings offers the prospect of smaller and optimized sample size, in the present study we define an anatomical imaging biomarker that could be objectively measured from micro-CT imaging data as an indicator of bone erosion in arthritis process. The well-characterized antigen-induced arthritis (AIA) model in rats was used. The animals were divided into 2 groups: arthritic disease control and arthritic having been administrated with the tumor necrosis factor alpha-blocking agent (Humira). Rats were sacrificed in the acute phase of AIA; peripheral blood and synovial tissue were collected for assessment of arthritis. Ex vivo micro-CT tomography of knee joints was performed at the Elettra synchrotron light source (Trieste, Italy). Overall, results from this study suggest that use of high-resolution micro-CT analysis coupled with meniscal ossicles bone parameters quantification provide a powerful combination to enhance data interpretation and assessment of disease-modifying drugs in an animal model of arthritis.

Highlights

  • It is increasingly recognized that early detection of bone erosion plays an important role in the overall evaluation of rheumatoid arthritis and in the choice of the correct treatment approach

  • We evaluated the bone status of knee joints in an antigen-induced arthritis (AIA) rat model by using an ex vivo high-resolution micro-Computed Tomography (CT) imaging approach

  • Intra-articular methylated bovine serum albumin injection was done in mBSA-sensitized rats and whole-articular imaging was performed acquiring micro-CT images 3–7 days post-injection, which correspond to the pick of the acute phase of inflammation

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Summary

Introduction

It is increasingly recognized that early detection of bone erosion plays an important role in the overall evaluation of rheumatoid arthritis and in the choice of the correct treatment approach. Results from this study suggest that use of high-resolution micro-CT analysis coupled with meniscal ossicles bone parameters quantification provide a powerful combination to enhance data interpretation and assessment of disease-modifying drugs in an animal model of arthritis. The characterization of the progression of RA in human is challenging because of limited clinical assessment tools and poor accessibility of disease tissue in the early phase and trough disease progression. In this context, animal models of RA have contributed greatly to the overall knowledge of principal pathogenic factors that causes bone and cartilage destruction, leading to important advances in medical products development[3]. New CT imaging modalities such as high resolution peripheral quantitative computed tomography (HR-pQCT) are promising for giving insight in the microarchitecture and geometry of the bone

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