title: Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts.
abstract: Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3'-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization.
authors.affiliation: Division of Medicine and Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: J H Duncan
authors.initials: JH
authors.lastname: Bassett
authors.forename: Alan
authors.initials: A
authors.lastname: Boyde
authors.forename: Peter G T
authors.initials: PG
authors.lastname: Howell
authors.forename: Richard H
authors.initials: RH
authors.lastname: Bassett
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Galliford
authors.forename: Marta
authors.initials: M
authors.lastname: Archanco
authors.forename: Holly
authors.initials: H
authors.lastname: Evans
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lawson
authors.forename: Peter
authors.initials: P
authors.lastname: Croucher
authors.forename: Donald L
authors.initials: DL
authors.lastname: St Germain
authors.forename: Valerie Anne
authors.initials: VA
authors.lastname: Galton
authors.forename: Graham R
authors.initials: GR
authors.lastname: Williams
mesh_terms: D000818:Animals; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D007037:Hypothyroidism / Q000473:pathology; D007453:Iodide Peroxidase / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism*; D010641:Phenotype; D013314:Stress, Mechanical; D055114:X-Ray Microtomography / Q000379:methods; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D000097564:Iodothyronine Deiodinase Type II