The role of DIO2 in joint biology and pathology.

Osteoarthritis is the most common chronic musculoskeletal disorder and a cause of serious morbidity and disablement, particularly in the elderly population. The development of osteoarthritis is very complex, involves several signaling pathways and the tissues in the joint, and is influenced by genetic, and acquired or environmental risk factors. Polymorphisms in the type II selenodeiodinase gene, DIO2, were recently associated with osteoarthritis. The gene codes for the type II iodothyronine deiodinase protein, an enzyme belonging to the iodothryonine deiodinase family. It activated thyroid hormone intracellularly by converting the pro-hormone thyroxine (T4) by outer ring deiodination to bioactive 3,3',5-triiodothyroninen (T3). We want to investigate the role of Dio2 in skeletal development, biology and pathology, with the emphasis on osteoarthritis. We will use different mouse models for osteoarthritis, combining gain or loss of function studies (in vivo tissue-specific, inducible overexpression of Dio2 and Dio2 knockout mice). We will also study the role of Dio2 in the growth and postnatal homeostasis of the skeleton. With this project, we want to corroborate the findings from human genetics research with functional studies and contribute to a better understanding of the pathological processes and identify possible therapeutic targets in osteoarthritis.

Keywords:Skeletal development, Bone, Arthritis, Cartilage, DIO2, Osteoarthritis

Disciplines:Orthopaedics