1 alpha,25-Dihydroxyvitamin D3 increases transforming growth factor and transforming growth factor receptor type I and II synthesis in human bone cells.
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.
Wu
Y
Y
Nephrology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Haugen
J D
JD
Zinsmeister
A R
AR
Kumar
R
R
D030201:Activin Receptors, Type I; D000906:Antibodies / Q000494:pharmacology; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D006131:Growth Inhibitors; D006133:Growth Substances; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D002117:Calcitriol