Endocrine Abstracts

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Osteoarthritis is a complex trait, and the currently reported genome-wide associated loci explain only a small proportion of its heritability. We previously developed and validated a rapid-throughput imaging pipeline to detect signs of osteoarthritis in the mouse knee joint. We utilised this pipeline to phenotype mutant mice generated by the International Knockout Mouse Consortium. We identified genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1 as a potential key regulator of disease progression. Using this pipeline, we were able to functionally characterize human osteoarthritis candidate genes in mouse models. Finally, we utilised this pipeline to phenotype mice with an osteoarthritis-associated polymorphism in the Dio2 gene and demonstrated a protective role in disease onset, with significant public health implications. This work aims to both accelerate functional gene discovery in osteoarthritis and facilitate drug discovery opportunities for this common, incapacitating chronic disease.