Abstract
To determine whether the inhibition of human osteoblast growth mediated by 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)D3) occurs as a result of changes in transforming growth factor (TGF) and TGF receptor synthesis, we examined the effects of 1 alpha,25(OH)2D3 on the synthesis of TGF beta and TGF-beta receptors. Treatment with 1 alpha,25(OH)2D3, but not vehicle, increased TGF-beta 2 concentrations in human osteoblast cell supernantants in a dose- and time-dependent manner. The increase in TGF-beta 2 concentrations was associated with an inhibition of osteoblast cell growth; antibodies directed against transforming growth factor beta partially blocked the inhibition of cellular growth mediated by 1 alpha,25-(OH)2D3 TGF-beta 2 gene transcription and TGF-beta 2 mRNA concentrations were increased in 1 alpha,25(OH)D3 but not in vehicle-treated cells. 1 alpha,25(OH)2D3 increased TGF-beta type I and type II receptor mRNA levels in osteoblasts. Increased expression of TGF-beta 2 and TGF-beta receptors by 1 alpha,25(OH)2D3 might account for the inhibition of human osteoblast growth seen following 1 alpha,25(OH)2D3 treatment.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activin Receptors, Type I*
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Antibodies / pharmacology
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Calcitriol / antagonists & inhibitors
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Calcitriol / immunology
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Calcitriol / pharmacology*
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Cell Line
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Cell-Free System
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Dose-Response Relationship, Drug
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Fetus
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Growth Inhibitors / antagonists & inhibitors
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Growth Inhibitors / immunology
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Growth Inhibitors / pharmacology
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Growth Substances / metabolism
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Humans
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Osteoblasts / cytology
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Osteoblasts / drug effects
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Osteoblasts / metabolism*
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Protein Serine-Threonine Kinases / biosynthesis*
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Protein Serine-Threonine Kinases / genetics
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / biosynthesis*
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Receptors, Transforming Growth Factor beta / genetics
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Transcription, Genetic / drug effects
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Transforming Growth Factor beta / biosynthesis*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / immunology
Substances
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Antibodies
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Growth Inhibitors
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Growth Substances
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RNA, Messenger
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Calcitriol