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Title of Journal: J Bone Miner Metab

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Abbravation: Journal of Bone and Mineral Metabolism

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Springer Japan

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DOI

10.1016/0141-1136(91)90007-u

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ISSN

1435-5604

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Effects of transgenic Pit1 overexpression on calc

Authors: Atsushi Suzuki Patrick Ammann Keiko NishiwakiYasuda Sahoko Sekiguchi Shogo Asano Shizuko Nagao Ryosuke Kaneko Masumi Hirabayashi Yutaka Oiso Mitsuyasu Itoh Joseph Caverzasio
Publish Date: 2009/10/01
Volume: 28, Issue: 2, Pages: 139-148
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Abstract

The type III inorganic phosphate Pi transporter Pit1 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 Pit1 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 wildtype 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 calvariaderived osteoblasts from Pit1 Tg was associated with a significantly decreased expression of alkaline phosphatase activity and a normal deposition and calcification of the collagenous matrix In 4monthold 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 Pit1 Tg rats were negatively correlated with serum fibroblast growth factor23 whereas 125dihydroxyvitamin D3 was not affected by Pit1 overexpression In conclusion transgenic Pit1 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 developmentWe thank S Troccaz Isabelle Badoud P Apostolides and Y Matsumoto for their expert technical assistance This study was supported by the Swiss National Science Foundation 3100AO112146 and GrantinAid for Scientific Research from the Ministry of Education Culture Sports Science and Technology of Japan No 15590987 and by the Cooperative Study Program of National Institute for Physiological Sciences Japan

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