title: Retinoic acid increases zif268 early gene expression in rat preosteoblastic cells.
abstract: In this study we demonstrate that retinoic acid (RA) increases the expression of transcription factor zif268 mRNA in primary cultures of fetal rat calvarial cells and in simian virus 40-immortalized clonal rat calvarial preosteoblastic cells (RCT-1), which differentiate in response to RA, but not in the more differentiated RCT-3 and ROS 17/2.8 cells. The increased expression of zif268 mRNA is rapid (maximal within 1 h), transient (returns to basal levels by 3 h), detectable at RA doses of 10(-12)M, and independent of protein synthesis. The relative stimulation of zif268 mRNA by RA was much larger than that of other early genes, including c-fos, c-jun, and junB. The rate of transcription of RA-stimulated RCT-1 cells, estimated by nuclear run-on assays, was elevated, suggesting that RA regulation of zif268 gene transcription was at least in part transcriptional. Moreover, RA stimulated the transcriptional activity of a Zif268CAT (chloramphenicol acetyltransferase) plasmid containing 632 bp of zif268 5' regulatory sequences in RCT-1 cells but not in the more differentiated RCT-3 cells. These in vitro data support the in vivo observations which localize zif268 and RA receptor-gamma transcripts to bone and cartilage during development, suggesting that both RA and zif268 may play a role in osteoblast differentiation.
authors.affiliation: Department of Bone Biology and Osteoporosis Research, Merck, Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: L J
authors.initials: LJ
authors.lastname: Suva
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: G A
authors.initials: GA
authors.lastname: Rodan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D017874:Immediate-Early Proteins; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D015342:DNA Probes; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014212:Tretinoin; D012313:RNA; D003513:Cycloheximide; D015500:Chloramphenicol O-Acetyltransferase