Hydrocortisone increases the rate of differentiation of cultured human osteoblasts.
Reduced bone formation is the main finding in glucocorticoid-induced osteoporosis. The aim of this study was to determine whether differentiation of cultured human osteoblasts is inhibited by high concentrations of hydrocortisone. We measured the levels of mRNAs for three markers of cellular differentiation, type 1 collagen (COL1), alkaline phosphatase (ALP), and osteocalcin (OC), in four lines of human osteoblasts from female donors cultured with doses of hydrocortisone from 0 microM to 4 microM. The change in ALP/COL1 mRNA ratio over a given time was used to determine the average rate of differentiation of the cells in a culture. Although basal expression profiles and their changes with time were different for the different cell lines, all cell lines showed a dose-dependent rise in the rate of increase of ALP mRNA relative to COL1 mRNA. However, increase in OC mRNA with time, seen here only in young donor hOBs, was significantly inhibited by 4 microM hydrocortisone, indicating that hydrocortisone can inhibit OC expression while promoting cellular differentiation. The data suggest that increasing concentrations of glucocorticoid, including concentrations similar to plasma levels in patients receiving oral glucocorticoid therapy, increase the rate of cellular differentiation.
Ireland
Deborah C
DC
University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, United Kingdom. dci20@mole.bio.cam.ac.uk
Bord
Sharyn
S
Beavan
Siân R
SR
Compston
Juliet E
JE
D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007223:Infant; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024042:Collagen Type I; D012333:RNA, Messenger; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D006854:Hydrocortisone