Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

Aims: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability.

Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents.

Background: Established MRI and emerging X-ray contrast agents for non-invasive imaging of articular cartilage rely on non-selective electrostatic interactions with negatively charged proteoglycans. These contrast agents have limited prognostic utility in diseases such as osteoarthritis (OA) due to the characteristic high turnover of proteoglycans. To overcome this limitation, we developed a radiocontrast agent that targets the type II collagen macromolecule in cartilage and used it to monitor disease progression in a murine model of OA.

Studying Osteoarthritis Pathogenesis in Mice.

With the increasing availability and complexity of mouse models of disease, either spontaneous or induced, there is a concomitant increase in their use in the analysis of pathogenesis. Among such diseases is osteoarthritis, a debilitating disease with few treatment options. While advances in our understanding of the pathogenesis of osteoarthritis has advanced through clinical investigations and genome-wide association studies, there is still a large gap in our knowledge, hindering advances in therapy.

Application of autofluorescence robotic histology for quantitative evaluation of the 3-dimensional morphology of murine articular cartilage.

Murine models of osteoarthritis (OA) are increasingly important for understating pathogenesis and for testing new therapeutic approaches. Their translational potential is, however, limited by the reduced size of mouse limbs which requires a much higher resolution to evaluate their articular cartilage compared to clinical imaging tools. In experimental models, this tissue has been predominantly assessed by time-consuming histopathology using standardized semi-quantitative scoring systems.

Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.

Objective: The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods.

Synchrotron- and laboratory-based X-ray phase-contrast imaging for imaging mouse articular cartilage in the absence of radiopaque contrast agents.

The mouse model of osteoarthritis (OA) has been recognized as the most promising research tool for the identification of new OA therapeutic targets. However, this model is currently limited by poor throughput, dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). We have recently shown that AC in the rat tibia can be imaged both in air and in saline solution using a laboratory system based on coded-aperture X-ray phase-contrast imaging (CAXPCi).

Visualization of small lesions in rat cartilage by means of laboratory-based x-ray phase contrast imaging.

Being able to quantitatively assess articular cartilage in three-dimensions (3D) in small rodent animal models, with a simple laboratory set-up, would prove extremely important for the development of pre-clinical research focusing on cartilage pathologies such as osteoarthritis (OA). These models are becoming essential tools for the development of new drugs for OA, a disease affecting up to 1/3 of the population older than 50 years for which there is no cure except prosthetic surgery. However, due to limitations in imaging technology, high-throughput 3D structural imaging has not been achievable in small rodent models, thereby limiting their translational potential and their efficiency as research tools.