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J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3691. [Epub ahead of print]

Slc20a2, encoding the phosphate transporter PiT2, is an important genetic determinant of bone quality and strength.

Author information

1
Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, F-44042, France.
2
Université de Nantes, UFR Odontologie, Nantes, F-44042, France.
3
Mouse Pipelines, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
4
Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London W12 0NN, UK.
5
CHU Nantes, PHU 4 OTONN, Nantes, F-44042, France.
6
The Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
7
St Vincent's Clinical School, Faculty of Medicine, UNSW Australia Sydney, NSW 2052, Australia.
8
CHU Nantes, Laennec Hospital, Nantes, F-44093, France.
9
Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.
10
Rheumatology Department, Soissons Hospital, 02200 Soissons, France.
11
Department of Neuroradiology, Rouen University Hospital, F-76000, Rouen, France.

Abstract

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 bone mineral density, 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. This article is protected by copyright. All rights reserved.

KEYWORDS:

ANIMAL MODELS (Genetic animal models); BONE MATRIX (Matrix mineralization); DISORDERS OF CALCIUM/PHOSPHATE METABOLISM (Other); GENETIC RESEARCH (Human association studies); ORTHOPAEDICS (Biomechanics)

PMID:
30721528
DOI:
10.1002/jbmr.3691

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