Mice with Hypomorphic Expression of the Sodium-Phosphate Cotransporter PiT1/Slc20a1 Have an Unexpected Normal Bone Mineralization
Open Access
- 13 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e65979
- https://doi.org/10.1371/journal.pone.0065979
Abstract
The formation of hydroxyapatite crystals and their insertion into collagen fibrils of the matrix are essential steps for bone mineralization. As phosphate is a main structural component of apatite crystals, its uptake by skeletal cells is critical and must be controlled by specialized membrane proteins. In mammals, in vitro studies have suggested that the high-affinity sodium-phosphate cotransporter PiT1 could play this role. In vivo, PiT1 expression was detected in hypertrophic chondrocytes of murine metatarsals, but its implication in bone physiology is not yet deciphered. As the complete deletion of PiT1 results in embryonic lethality at E12.5, we took advantage of a mouse model bearing two copies of PiT1 hypomorphic alleles to study the effect of a low expression of PiT1 on bone mineralization in vivo. In this report, we show that a 85% down-regulation of PiT1 in long bones resulted in a slight (6%) but significant reduction of femur length in young mice (15- and 30-day-old). However, despite a defect in alcian blue / alizarin red S and Von Kossa staining of hypomorphic 1-day-old mice, using X-rays micro-computed tomography, energy dispersive X-ray spectroscopy and histological staining techniques we could not detect differences between hypomorphic and wild-type mice of 15- to 300-days old. Interestingly, the expression of PiT2, the paralog of PiT1, was increased 2-fold in bone of PiT1 hypomorphic mice accounting for a normal phosphate uptake in mutant cells. Whether this may contribute to the absence of bone mineralization defects remains to be further deciphered.Keywords
This publication has 37 references indexed in Scilit:
- Regulation of cell proliferation and cell density by the inorganic phosphate transporter PiT1Cell Division, 2012
- Identification of a Novel Transport-independent Function of PiT1/SLC20A1 in the Regulation of TNF-induced ApoptosisPublished by Elsevier BV ,2010
- The Phosphate Transporter PiT1 (Slc20a1) Revealed As a New Essential Gene for Mouse Liver DevelopmentPLOS ONE, 2010
- Intestinal Npt2b Plays a Major Role in Phosphate Absorption and HomeostasisJournal of the American Society of Nephrology, 2009
- Identification of a Novel Function of PiT1 Critical for Cell Proliferation and Independent of Its Phosphate Transport ActivityJournal of Biological Chemistry, 2009
- Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: Indications for an amorphous precursor phaseProceedings of the National Academy of Sciences of the United States of America, 2008
- Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone MineralizationMolecular and Cellular Biology, 2007
- Enhanced Expression of the Inorganic Phosphate Transporter Pit-1 Is Involved in BMP-2–Induced Matrix Mineralization in Osteoblast-Like CellsJournal of Bone and Mineral Research, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red STeratology, 1980