TY - JOUR
T1 - Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism
AU - Suzuki, Atsushi
AU - Ammann, Patrick
AU - Nishiwaki-Yasuda, Keiko
AU - Sekiguchi, Sahoko
AU - Asano, Shogo
AU - Nagao, Shizuko
AU - Kaneko, Ryosuke
AU - Hirabayashi, Masumi
AU - Oiso, Yutaka
AU - Itoh, Mitsuyasu
AU - Caverzasio, Joseph
N1 - Funding Information:
We 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 (3100AO-112146) and Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 15590987), and by the Co-operative Study Program of National Institute for Physiological Sciences, Japan.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77952532130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952532130&partnerID=8YFLogxK
U2 - 10.1007/s00774-009-0121-3
DO - 10.1007/s00774-009-0121-3
M3 - Article
C2 - 19795094
AN - SCOPUS:77952532130
SN - 0914-8779
VL - 28
SP - 139
EP - 148
JO - Journal of Bone and Mineral Metabolism
JF - Journal of Bone and Mineral Metabolism
IS - 2
ER -
