Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism.
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 D(3) 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.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. aslapin@fujita-hu.ac.jp
Atsushi
A
Suzuki
Patrick
P
Ammann
Keiko
K
Nishiwaki-Yasuda
Sahoko
S
Sekiguchi
Shogo
S
Asano
Shizuko
S
Nagao
Ryosuke
R
Kaneko
Masumi
M
Hirabayashi
Yutaka
Y
Oiso
Mitsuyasu
M
Itoh
Joseph
J
Caverzasio
D000409:Alanine / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000097:blood; D006882:Hydroxyapatites / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D011859:Radiography; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D012886:Skull / Q000166:cytology / Q000378:metabolism; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D013977:Tibia / Q000166:cytology / Q000000981:diagnostic imaging
C505605:Fgf23 protein, rat; D006882:Hydroxyapatites; D010281:Parathyroid Hormone; D010710:Phosphates; C493587:Slc20a1 protein, mouse; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D005346:Fibroblast Growth Factors; D000469:Alkaline Phosphatase; D002117:Calcitriol; D000409:Alanine; D002118:Calcium