Thyroid hormone metabolism in skeletal development and adult bone maintenance

Metabolism of thyroid hormones by the type 2 and type 3 iodothyronine deiodinases (D2, D3) in T3-responsive target cells is a sophisticated mechanism that helps to maintain local T3 concentrations and facilitates T3 action in a cell-specific manner that is independent of circulating thyroid hormone concentrations. Recent findings have demonstrated an essential physiological role for the thyroid hormone-activating enzyme D2 in the optimization of bone mineralization and strength. Emerging population studies have also identified the genes encoding D2 and the thyroid hormone-inactivating enzyme D3 as susceptibility loci for osteoarthritis. These new data reveal an essential role for the local control of T3 availability in osteoblasts and chondrocytes during maintenance and repair of bone and cartilage.