Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

被引：110

作者：

Bassett, J. H. Duncan ^{[1
,2
]}

Boyde, Alan ^{[3
]}

Howell, Peter G. T. ^{[3
,4
]}

Bassett, Richard H. ^{[5
]}

Galliford, Thomas M. ^{[1
,2
]}

Archanco, Marta ^{[1
,2
]}

Evans, Holly ^{[6
]}

Lawson, Michelle A. ^{[6
]}

Croucher, Peter ^{[6
]}

Germain, Donald L. St. ^{[7
,8
]}

Galton, Valerie Anne ^{[7
,8
]}

Williams, Graham R. ^{[1
,2
]}

机构：

[1] Hammersmith Hosp, Mol Endocrinol Grp, Div Med, London W12 0NN, England

[2] Hammersmith Hosp, MRC, Ctr Clin Sci, Imperial Coll London, London W12 0NN, England

[3] Queen Mary Univ London, Inst Dent, Barts & London Sch Med, London E1 1BB, England

[4] UCL, Div Restorat Dent Sci, Eastman Dent Inst, London WC1E 6BT, England

[5] UCL, Dept Civil & Environm Engn, London WC1E 6BT, England

[6] Univ Sheffield, Mellanby Ctr Bone Res, Dept Human Metab, Sheffield S10 2RX, S Yorkshire, England

[7] Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA

[8] Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 16期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

thyroid hormone metabolism; fracture; hypothyroidism; bone formation; skeleton; THYROID-HORMONE; 3,5,3'-TRIIODOTHYRONINE CONVERSION; TARGETED DISRUPTION; MICE; THYROXINE; SELENODEIODINASE; HYPERTHYROIDISM; HYPOTHYROIDISM; DIFFERENTIATION; CHONDROCYTES;

D O I：

10.1073/pnas.0911346107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：7604 / 7609

页数：6

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