Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength

被引：32

作者：

Beck-Cormier, Sarah ^{[1
,2
]}

Lelliott, Christopher J. ^{[3
]}

Logan, John G. ^{[4
]}

Lafont, David T. ^{[3
]}

Merametdjian, Laure ^{[1
,2
,5
]}

Leitch, Victoria D. ^{[4
]}

Butterfield, Natalie C. ^{[4
]}

Protheroe, Hayley J. ^{[4
]}

Croucher, Peter I. ^{[6
,7
]}

Baldock, Paul A. ^{[6
,7
]}

Gaultier-Lintia, Alina ^{[8
]}

Maugars, Yves ^{[1
,5
]}

Nicolas, Gael ^{[9
,10
,11
]}

Banse, Christopher ^{[12
]}

Normant, Sebastien ^{[13
]}

Magne, Nicolas ^{[13
]}

Gerardin, Emmanuel ^{[13
]}

Bon, Nina ^{[1
,2
]}

Sourice, Sophie ^{[1
,2
]}

Guicheux, Jerome ^{[1
,2
,5
]}

Beck, Laurent ^{[1
,2
]}

Williams, Graham R. ^{[4
]}

Bassett, J. H. Duncan ^{[4
]}

机构：

[1] Univ Nantes, Ecole Natl Vet Agroalimentaire & Alimentat, INSERM, UMR 1229 Regenerat Med & Skeleton RMeS,Nantes Atl, Nantes, France

[2] Univ Nantes, Unite Format & Rech UFR Odontol, Nantes, France

[3] Wellcome Trust Sanger Inst, Mouse Pipelines, Hinxton, England

[4] Imperial Coll London, Dept Med, Mol Endocrinol Lab, London, England

[5] CHU Nantes, Poles Hosp Univ PHU4, OTONN, Nantes, France

[6] Garvan Inst Med Res, Sydney, NSW, Australia

[7] Univ New South Wales UNSW Australia, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia

[8] CHU Nantes, Laennec Hosp, Nantes, France

[9] Univ Rouen Normandie UNIROUEN, INSERM, U1245, Rouen, France

[10] Rouen Univ Hosp, Dept Genet, Rouen, France

[11] Ctr Natl Reference Malad Alzheimer Jeunes CNR MAJ, Normandy Ctr Genom & Personalized Med, Rouen, France

[12] Soissons Hosp, Dept Rheumatol, Soissons, France

[13] Rouen Univ Hosp, Dept Neuroradiol, Rouen, France

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2019年 / 34卷 / 06期

基金：

英国惠康基金;

关键词：

ANIMAL MODELS (GENETIC ANIMAL MODELS); BONE MATRIX (MATRIX MINERALIZATION); DISORDERS OF CALCIUM; PHOSPHATE METABOLISM (OTHER); GENETIC RESEARCH (HUMAN ASSOCIATION STUDIES); ORTHOPAEDICS (BIOMECHANICS); MATRIX VESICLES; MINERAL DENSITY; EXPRESSION; GROWTH; CALCIFICATION; IDENTIFICATION; CELLS; OSTEOPOROSIS; BIOGENESIS; ROLES;

D O I：

10.1002/jbmr.3691

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2(-/-) mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2(-/-) mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. (c) 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

引用

页码：1101 / 1114

页数：14

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