HELIX-LOOP-HELIX-TYPE TRANSCRIPTION FACTOR (HES-1) IS EXPRESSED IN OSTEOBLASTIC CELLS, SUPPRESSED BY 1,25(OH)(2) VITAMIN-D-3, AND MODULATES1,25(OH)(2) VITAMIN-D-3 ENHANCEMENT OF OSTEOPONTIN GENE-EXPRESSION
M. Matsue et al., HELIX-LOOP-HELIX-TYPE TRANSCRIPTION FACTOR (HES-1) IS EXPRESSED IN OSTEOBLASTIC CELLS, SUPPRESSED BY 1,25(OH)(2) VITAMIN-D-3, AND MODULATES1,25(OH)(2) VITAMIN-D-3 ENHANCEMENT OF OSTEOPONTIN GENE-EXPRESSION, Bone, 20(4), 1997, pp. 329-334
The active form of vitamin D, 1,25(OH)(2) vitamin D-3 (D-3), is a pote
nt modulator of osteoblastic function, In this study, we examined, the
expression of a negative type basic helix-loop-helix transcription fa
ctor, HES 1, in osteoblastic cells and the regulation of its expressio
n by D-3, We found that HES-1 is expressed as a 1.7 kb mRNA in rat ost
eoblastic osteosarcoma ROS17/2.8 cells, Treatment with D-3 suppressed
HES-1 mRNA levels by about 50%, This suppression was observed within 2
4 h and lasted for at least 48 h, The suppressive effect was dose-depe
ndent starting at 10(-9) mol/L and saturated at 10(-8) mol/L, The vita
min D-3 suppression of HES-1 mRNA level was blocked by actinomycin D a
s well as cycloheximide, suggesting the involvement of transcriptional
control, which requires new protein synthesis, Proteins in the crude
nuclear extracts prepared from ROS17/ 2.8 cells bound to the N-box seq
uence (CACNAG), To examine the function of HES-1 in osteoblasts, HES-1
was overexpressed in ROS17/2.8 cells, Overexpression of HES-1 suppres
sed the vitamin D-dependent upregulation of osteopontin gene expressio
n in these cells, Vitamin D suppression of HES-1 gene expression was a
lso observed in normal rat calvaria-derived osteoblast-enriched cells,
These results indicate that HES-1 is expressed in osteoblastic cells
and is involved in vitamin D-3 regulation of osteoblastic gene express
ion. (C) 1997 by Elsevier Science Inc.