Osteoarthritis is the most common cause of joint destruction. It causes debilitating pain and disability, yet no drugs are currently available to prevent its onset or progression. The disease is characterised by loss or destruction of cartilage, structural bone abnormalities and chronic joint inflammation.
A recent study, published in Nature, has developed and validated a rapid-throughput imaging technique to identify abnormal joint phenotypes. They hope this screen will accelerate functional gene discovery in osteoarthritis.
Using a combination of methods, the researchers designed a mouse joint phenotyping pipeline. To validate their pipeline, they screened 50 randomly selected mouse lines from the International Mouse Phenotyping Consortium (IMPC). Overall, 14 genes were identified that may have a functional role in osteoarthritis progression. The pipeline provided a reliable and sensitive detection of increased cartilage damage and features of osteoarthritis.
Promisingly, their screen was able to identify early features of age-related joint degeneration in 1 year old animals, 3 months younger than previous screens were able to detect. Furthermore, their pipeline was ⅓ of the cost and took ⅙ of the time compared to the current gold standard test. It may also be used in future studies to identify genes which protect joints against age related degeneration.
Protection Against Osteoarthritis
The researchers also identified a gene which may play a protective role against the development of osteoarthritis. The Ala92 variant of the DIO2 gene prevents conversion of the prohormone T4 to the active hormone T3. This conversion has been associated with osteoarthritis, but the results are controversial.
Interestingly, levothyroxine – a drug used to treat hypothyroidism – increases the expression of this allele. However, other studies have suggested this drug may have a detrimental long term effect on the protection of cartilage. This has important public health implications as levothyroxine is the 3rd most commonly prescribed drug in the UK.
Overall, the researchers demonstrated that their joint phenotyping method has broad applications in osteoarthritis research. They hope it will accelerate functional gene discovery, advance understanding of disease pathogenesis and identify new drug targets for this debilitating disease.
Picture Credit: Unsplash