Calcium and insulin-like growth factor I stimulation of sodium-dependent phosphate transport and proliferation of cultured rat osteoblasts.
Calcium (Ca) stimulates proliferation of osteoblasts in vitro, an effect proposed to be mediated by IGF I. Addition of 1 mM Ca or of 1 nM IGF I to the medium (0.3 mM Ca) of a rat bone-derived cell line, PyMS, stimulated not only DNA synthesis but also sodium-dependent (Nad) phosphate (Pi) uptake, the latter, within 2 h. These cells barely express and produce IGF I. IGF binding protein-3 which inhibits IGF action decreased neither basal nor Ca-stimulated but IGF I-stimulated NadPi transport and DNA synthesis, indicating that Ca stimulated NadPi transport and DNA synthesis independently of IGF I. The effects of Ca and IGF I on DNA synthesis were additive. 1 microM nifedipine blocked IGF I- and Ca-stimulated DNA synthesis but not NadPi transport, suggesting that Ca influx is not mediating the NadPi transport-enhancing IGF I signal but is required for IGF I-induced osteoblast proliferation.
Schmid
C
C
Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, Zürich, CH-8091, Switzerland.
Keller
C
C
Schläpfer
I
I
Veldman
C
C
Zapf
J
J
D000409:Alanine / Q000493:pharmacokinetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects*; D028044:Phosphate-Binding Proteins; D010710:Phosphates / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D012964:Sodium; D017526:Receptor, IGF Type 1; D000469:Alkaline Phosphatase; D009543:Nifedipine; D000409:Alanine; D002118:Calcium