Role of the sodium-dependent phosphate transporter PIT1 in bone growth in vivo

Abstract

Many studies have shown the importance of PiT1 in mineralizing processes in vitro. However, although PiT1 is preferentially expressed in growth plate chondrocytes [1], evidence of its in vivo role in bone and cartilage is missing. To gain further insights into this role, we used a mice model that only expresses 15% of PiT1 mRNA (hypomorphic mice). We have already demonstrated that newborn hypomorphic mice are smaller, displaying an affected growth compared to wild-type mice [2]. Moreover, newborn alcian blue/alizarin red skeleton staining revealed an impaired mineralization of these mice. To further investigate the implication of PiT1 in bone growth, we performed a histomorphometric and histological characterization of mice femurs from male and female mice, divided into 4 different age groups (15, 30, 90 and 300 days) with 5 mice per group. Our preliminary results show that an in vivo reduction of PiT1 expression induces an alteration in the histomorphometric parameters such as femur length and BV/TV. However, these differences are compensated after the first 30 days of age. Consistent with this hypothesis, we could not evidence histological differences on Goldner staining femur sections between wild-type and hypomorphic mice. Despite the fact that they only express 15% of PiT1, serum analyses of hypomorphic mice indicate that they exhibit a normophosphatemia, suggesting that PiT1 is not essential for a normal renal Pi reabsorption. However, young hypomorphic mice display a hyperphosphaturia which could be related to an impaired bone mineralization. This hypothesis will be paid attention in further experiments. The whole of these results suggest that a reduction of PiT1 expression in vivo leads to bone abnormalities during the first steps of bone growth and that a compensatory phenomenon may be involved at later stages. A conditional tissue-specific inactivation of PiT1 expression in bone or cartilage should be paid further attention to decipher the in vivo role of PiT1 in the skeleton. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.