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Mouse models of osteoarthritis: modelling risk factors and assessing outcomes
Hang Fang and Frank Beier
Abstract | Osteoarthritis (OA) is a prevalent musculoskeletal disease that results in pain and low qualityof life for patients, as well as enormous medical and socioeconomic burdens. The molecular mechanisms responsible for the initiation and progression of OA are still poorly understood. As such, mouse models of the disease are having increasingly important roles in OA research owing to the advancements of microsurgical techniques and the use of genetically modified mice, as well as the development of novel assessment tools. In this Review, we discuss available mouse models of OA and applicable assessment tools in studies of experimental OA.
Fang, H. & Beier, F. Nat. Rev. Rheumatol. 10, 413421 (2014); published online 25 March 2014; http://www.nature.com/doifinder/10.1038/nrrheum.2014.46
Web End =doi:10.1038/nrrheum.2014.46
Introduction
Osteoarthritis (OA) is a musculoskeletal disease with worldwide prevalence, causing disability to millions and imposing enormous medical and socioeconomic burdens.1 OA is now considered a disease of the whole joint, characterized by articular cartilage degeneration, subchondral bone remodelling, osteophyte formation and synovial changes.2 No drug has been approved by the FDA or any other agencies worldwide for OA disease modification; available drugs only provide sympto matic relief of pain, and joint replacement is the only choice eventually. This lack of disease-modifying drugs is partly attributable to our poor understanding of the mechanisms initiating and driving OA. In addition, the inadequacy of radio graphy to detect early disease stages and disease progression over time3 presents a major hurdle in testing such drugs in patients. Early diagnosis is still a major issue in patients with OA, mandating the use of animal models to explore the molecular mechanisms leading to OA, to further define the risk factors that initiate or promote the condition, and to discover diagnostic biomarkers and therapeutic targets. Mouse models have an increasingly prominent role in OA research, primarily because of the development of sophisticated strategies for genetic manipulation that are currently only available for use in mice. These genetic models can be combined with surgery and dietary or exercise regimens to mimic human OA risk factors, to gain insights into the disease process and the role of speci
fic genes. Mice are reasonably inexpensive to house, and...