Abstract
BackgroundInflammatory arthritis is a chronic disease, resulting in synovitis and subchondral and bone area destruction, which can severely affect a patient’s quality of life. The most common form of inflammatory arthritis is rheumatoid arthritis (RA) in which many of the disease mechanisms are not well understood. The collagen-induced arthritis (CIA) mouse model is similar to RA as it exhibits joint space narrowing and bone erosion as well as involves inflammatory factors and cellular players that have been implicated in RA pathogenesis. Quantitative data for disease progression in RA models is difficult to obtain as serum blood markers may not always reflect disease state and physical disease indexes are subjective. Thus, it is important to develop tools to objectively assess disease progression in CIA.ResultsMicro-CT (Computed Tomography) is a relatively mature technology that has been used to track a variety of anatomical changes in small animals. In this study, micro-CT scans of several joints of control and CIA mice were acquired at 0, 4, 7, and 9 weeks after the immunization with collagen type II. Each micro-CT scan was analyzed by applying a segmentation algorithm to individual slices in each image set to provide 3-dimensional representations of specific bones including the humerus, femur, and tibia. From these representations, the volume and mean density of these bones were measured and compared. This analysis showed that both the volume and the density of each measured bone of the CIA mice were significantly smaller than those of the controls at week 7.ConclusionsThis study demonstrates that micro-CT can be used to quantify bone changes in the CIA mouse model as an alternative to disease index assessments. In conclusion, micro-CT could be useful as a non-invasive method to monitor the efficacy of new treatments for RA tested in small animals.
Highlights
Inflammatory arthritis is a chronic disease, resulting in synovitis and subchondral and bone area destruction, which can severely affect a patient’s quality of life
Structural damages caused by rheumatoid arthritis (RA) have been assessed using conventional radiography to detect cortical bone erosion, joint space narrowing, and peri-articular osteoporosis [8]
Other non-invasive clinical assessment tools include magnetic resonance imaging (MRI) and ultrasound (US), but these have proven even less sensitive and accurate compared with computed tomography (CT) for detecting bone erosion [10,11]
Summary
Inflammatory arthritis is a chronic disease, resulting in synovitis and subchondral and bone area destruction, which can severely affect a patient’s quality of life. The collageninduced arthritis (CIA) mouse model is similar to RA as it exhibits joint space narrowing and bone erosion as well as involves inflammatory factors and cellular players that have been implicated in RA pathogenesis. Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis, consisting of almost 50% of the Structural damage in RA typically includes cartilage and bone reabsorption. Structural damages caused by RA have been assessed using conventional radiography to detect cortical bone erosion, joint space narrowing, and peri-articular osteoporosis [8]. Conventional radiography is not sensitive enough to assess early joint erosion or inflammatory soft tissue damage and is limited by the two-dimensional visualization which results in projection and plane of section errors [8]. It has been suggested that micro-CT may yield better results in interpreting and identifying the damaged area in bones of small joints, because micro-CT is reproducible and quantitative [12]
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