Dexamethasone enhancement of betaglycan (TGF-beta type III receptor) gene expression in osteoblast-like cells.
Betaglycan (type III transforming growth factor-beta (TGF-beta) receptor) is a cell surface heparan/chondroitin sulfate proteoglycan that binds TGF-beta via its core protein and is abundantly expressed in osteoblastic cells. A previous report (Centrella et al., Mol. Cell. Biol. 11, 4490-4496, 1991) showed post-translational enhancement by glucocorticoid of TGF-beta binding to betaglycan. Upon the availability of the betaglycan cDNA, we investigated the effects of a glucocorticoid analogue, dexamethasone, on the regulation of betaglycan expression in osteoblast-like cells. Betaglycan mRNA was expressed as an approximately 6-kb band in MC3T3-E1 cells. The betaglycan mRNA level was enhanced severalfold by dexamethasone in these cells. The effect of dexamethasone on the betaglycan mRNA level was observed within 9 h and was sustained at least up to 48 h. The dexamethasone effect was dose-dependent, with a saturation concentration at 10(-7) M. Among the steroid hormones examined, dexamethasone exhibited the most potent effect on betaglycan mRNA expression, while retinoic acid also enhanced it moderately. Dexamethasone enhancement of betaglycan mRNA expression was blocked by actinomycin D, but it was not blocked by cycloheximide. Cross-linking experiments showed that dexamethasone treatment increased the binding of radiolabeled TGF-beta 1 to betaglycan, but did not affect binding to the type II receptor. A similar dexamethasone enhancement of betaglycan mRNA expression was also observed in a preosteoblast-like cell line, RCT1. These results suggest that dexamethasone enhances betaglycan expression at least in part via transcriptional events in osteoblasts and this would be one of the target points of glucocorticoid regulation of bone metabolism.
Nakayama
H
H
Department of Molecular Pharmacology, Tokyo Medical University, Japan.
Ichikawa
F
F
Andres
J L
JL
Massagué
J
J
Noda
M
M
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
D008565:Membrane Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide