Mice with Hypomorphic Expression of the Sodium-Phosphate Cotransporter PiT1/Slc20a1 Have an Unexpected Normal Bone Mineralization

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.
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Annabelle Bourgine, Paul Pilet, Sara Diouani, Sophie Sourice, Julie Lesoeur, et al.. Mice with Hypomorphic Expression of the Sodium-Phosphate Cotransporter PiT1/Slc20a1 Have an Unexpected Normal Bone Mineralization. PLoS ONE, Public Library of Science, 2013, 8 (6), pp.65979. ⟨10.1371/journal.pone.0065979⟩. ⟨inserm-01847748⟩

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