title: 1Alpha25(OH)2D3 interferes with retinoic acid-induced inhibition of c-fos gene expression for AP-1 formation in osteoblastic cells.
abstract: Our previous studies demonstrated retinoic acid (RA) inhibition of activation protein-1 (AP-1) formation in TNF-alpha-treated osteoblastic MC3T3-E1 cells via c-fos suppression. In the present study, we observed that 1alpha25(OH)2D3 was able to interfere at the transcriptional level with RA inhibition of TNF-alpha-induced c-fos gene expression in cells when the cells were incubated with the vitamin for 24 hr before the RA treatment. 22-Oxa-1,25(OH)2D3 (OCT), an analog derivative of 1alpha25(OH)2D3, having high affinity for the vitamin D3 receptor (VDR), also interfered with the RA-induced inhibition of c-fos gene expression in the TNF-alpha-treated cells. In contrast, this was not the case for 24,25(OH)2D3. Moreover, we observed that the interfering effect was clearly blocked by pretreatment with VDR antisense oligonucleotide. 1alpha25(OH)2D3 interfered with RA inhibition of the TPA-response element binding activity of AP-1 in the cytokine-treated cells. Furthermore, 1alpha25(OH)2D3 actually blocked the AP-1-mediated gene expression of monocyte chemoattractant JE/MCP-1 induced in the cytokine-treated cells. The present study suggests a regulatory interference by 1alpha25(OH)2D3 for RA inhibition of TNF-alpha-induced AP-1 activity in osteoblasts.
authors.affiliation: Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan. takesita@dent.meikai.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yasuda
authors.forename: Masami
authors.initials: M
authors.lastname: Ishida
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Ochiai
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015152:Blotting, Northern; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology*; D030181:Vitamin D Response Element / Q000187:drug effects / Q000235:genetics
chemical_list: C116441:2-methyl-1,25-dihydroxyvitamin D3; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D016373:DNA, Antisense; D018167:Receptors, Calcitriol; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D014212:Tretinoin; D002117:Calcitriol; C051883:maxacalcitol