Evidence that anabolic effects of PTH on bone require IGF-I in growing mice

Citation
N. Miyakoshi et al., Evidence that anabolic effects of PTH on bone require IGF-I in growing mice, ENDOCRINOL, 142(10), 2001, pp. 4349-4356
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINOLOGY
ISSN journal
0013-7227 → ACNP
Volume
142
Issue
10
Year of publication
2001
Pages
4349 - 4356
Database
ISI
SICI code
0013-7227(200110)142:10<4349:ETAEOP>2.0.ZU;2-5
Abstract
Although it has been established that PTH exerts potent anabolic effects on bone in animals and humans, the mechanism of PTH action on bone remains co ntroversial. Based on the previous findings that PTH treatment increased pr oduction of IGF-I in bone cells and that PTH effects on bone cells in vitro were blocked by IGF-I-blocking antibodies, we proposed that IGF-I action i s required for the stimulatory effects of PTH on bone formation. To test th is hypothesis, we evaluated the effects of PTH on bone formation parameters in growing mice lacking functional IGF-I genes. Five-week-old IGF-I(-/-) m ice and wild-type littermates were given daily se injections of 160 mug/kg body weight of PTH (1-34) or vehicle for 10 d. In wildtype animals, PTH cau sed a significant increase in serum osteocalcin levels (113%), serum alkali ne phosphatase activity (48%), and alkaline phosphatase activity in femoral bone ex-tracts (> 80%), compared with the vehicle-treated control group. I n contrast, in IGF-I(-/-) mice, there was no significant effect of PTH on a ny bone formation parameters. PTH treatment increased total bone mineral de nsity, as evaluated by peripheral quantitative computer tomography, at the distal metaphysis of the femur by 40% in wild-type mice, but it had no effe ct on bone mineral density in mice lacking functional IGF-I genes. In vitro studies using osteoblasts derived from control and IGF-I(-/-) mice reveale d that PTH treatment increased cell number in osteoblasts derived from IGF- I knockout mice in the presence of exogenously added IGF-I but not without IGF-I. These data to our knowledge provide the first direct evidence that t he anabolic effects of PTH on bone formation in vivo require IGF-I action i n growing mice.