Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism

Atsushi Suzuki, Patrick Ammann, Keiko Nishiwaki-Yasuda, Sahoko Sekiguchi, Shogo Asano, Shizuko Nagao, Ryosuke Kaneko, Masumi Hirabayashi, Yutaka Oiso, Mitsuyasu Itoh, Joseph Caverzasio

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Abstract

The type III inorganic phosphate (Pi) transporter Pit-1 was previously found to be preferentially expressed in developing long bones. Several studies also described a regulation of its expression in cultured bone cells by osteotropic factors, suggesting a role of this transporter in bone metabolism. In the present study, we investigated the effects of the transgenic overexpression of Pit-1 in Wistar male rats on calcium phosphate and bone metabolism. A threefold increase and doubling of Pi transport activity were recorded in primary cultured osteoblastic cells derived from calvaria of two transgenic (Tg) lines compared with wild-type littermates (WT), respectively. Skeletal development was not affected by the transgene, and bone mass, analyzed by DXA, was slightly decreased in Tg compared with WT. Enhanced Pi uptake in calvaria-derived osteoblasts from Pit-1 Tg was associated with a significantly decreased expression of alkaline phosphatase activity and a normal deposition and calcification of the collagenous matrix. In 4-month-old adult Tg rats, serum Pi and renal Pi transport were increased compared with WT. The decrease of serum Ca concentration was associated with increased serum parathyroid hormone levels. Variations in serum Pi in Pit-1 Tg rats were negatively correlated with serum fibroblast growth factor-23, whereas 1,25-dihydroxyvitamin D3 was not affected by Pit-1 overexpression. In conclusion, transgenic Pit-1 overexpression in rats affected bone and calcium phosphate metabolism. It also decreased alkaline phosphatase activity in osteoblasts without influencing bone matrix mineralization as well as skeletal development.

Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalJournal of Bone and Mineral Metabolism
Volume28
Issue number2
DOIs
Publication statusPublished - 03-2010

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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    Suzuki, A., Ammann, P., Nishiwaki-Yasuda, K., Sekiguchi, S., Asano, S., Nagao, S., Kaneko, R., Hirabayashi, M., Oiso, Y., Itoh, M., & Caverzasio, J. (2010). Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism. Journal of Bone and Mineral Metabolism, 28(2), 139-148. https://doi.org/10.1007/s00774-009-0121-3