Effects of estrogen and parathyroid hormone on osteoblastic activity via regulating the binding activity of insulin-like growth factor binding protein-4 in SaOS-2 cells: implications for the pathogenesis of postmenopausal osteoporosis.
The cellular mechanisms involved in the accelerated bone loss occurring in association with estrogen deprivation as seen following the menopause have not been fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of osteoblasts and one of its binding protein, insulin-like growth factor binding protein-4 (IGFBP-4), binds to IGF-I and suppresses its biological activity. We have therefore studied the effects of 17 beta-estradiol and parathyroid hormone (PTH) on binding activity of IGFBP-4 and osteoblastic activity using SaOS-2 osteoblastic cells. DNA and collagen synthesis were enhanced by IGF-I or 17 beta-estradiol and suppressed by PTH in a concentration dependent manner. The inhibitory effect of PTH on DNA and collagen synthesis was abolished by the presence of IGF-I or 17 beta-estradiol. The binding activity of IGFBP-4 was stimulated 2-fold by 10 nM PTH, while this PTH-induced IGFBP-4 production was completely inhibited by the addition of 17 beta-estradiol. The stimulated DNA and collagen synthesis by IGF-I or 17 beta-estradiol were inhibited by IGFBP-4 in a concentration dependent manner. The simplest explanation is that 17 beta-estradiol suppressed the inhibitory effect of PTH on osteoblastic activity by inhibiting the PTH-induced increment of IGFBP-4 binding activity in SaOS-2 cells.
Kudo
Y
Y
Department of Obstetrics and Gynecology, Tokyo Women's Medical College, Japan.
Itatsu
S
S
Iwashita
M
M
Iguchi
T
T
Takeda
Y
Y
D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*
D018974:Insulin-Like Growth Factor Binding Protein 4; D010281:Parathyroid Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I