Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5.
Although there is clinical evidence showing that combined therapy with parathyroid hormone (PTH) and estrogen is additively effective in increasing the bone mass of patients with osteoporosis, the mechanism of the interaction between these hormones remains unclear. The present study was performed to determine whether estrogen would affect osteoblast proliferation and function modulated by PTH in human osteoblastic SaOS-2 cells. Human PTH-(1-34) significantly inhibited [(3)H]thymidine (TdR) incorporation, which was attenuated by 24 h pretreatment with 10(-10) to 10(-7) M 17 beta-estradiol (17 beta-E(2)) in a concentration-dependent manner. PTH significantly stimulated alkaline phosphatase (ALP) activity, collagen synthesis and type-1 procollagen mRNA expression after pretreatment with 17 beta-E(2 )in these cells. Tamoxifen, an anti-estrogen, antagonized these 17 beta-E(2)-induced effects. Pretreatment with insulin-like growth factor-I (IGF-I) mimicked estrogen action, and coincubation of 3 microg/ml anti-IGF-I antibody antagonized the effects of 17 beta-E(2 )as well as those of IGF-I. In the presence of 17 beta-E(2 )pretreatment, PTH strongly stimulated IGF-binding protein (IGFBP)-5 mRNA expression in these cells, and recombinant IGFBP-5 increased type-1 procollagen mRNA expression and ALP activity. In conclusion, estrogen attenuates PTH-induced inhibition of osteoblast proliferation and PTH stimulates osteoblast function in the presence of estrogen pretreatment. IGF-I and/or IGFBP-5 seemed to be involved in the estrogen-induced modulation of PTH action on osteoblast proliferation and function.
Nasu
M
M
Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Sugimoto
T
T
Kaji
H
H
Chihara
K
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D018975:Insulin-Like Growth Factor Binding Protein 5; D010281:Parathyroid Hormone; D011347:Procollagen; D012333:RNA, Messenger; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase