Regulation of bone sialoprotein gene transcription by steroid hormones.
During the initial formation of bone, dentine and cementum in tooth morphogenesis, fully differentiated osteoblasts, odontoblasts and cementoblasts express bone sialoprotein (BSP), a mineralized tissue-specific acidic glycoprotein that has been implicated in the nucleation of hydroxyapatite crystal growth. The expression of BSP is regulated by steroid hormones that modulate mineralized tissue formation. Thus, the transcription of the BSP gene is induced by glucocorticoids in association with osteoblast differentiation and glucocorticoids also stimulate the expression of BSP in differentiated osteoblasts. In contrast, however, vitamin D3 suppresses bone formation and abrogates the expression of BSP. Our studies, using the osteoblastic cell lines ROS 17/2.8 and UMR 106-06, have revealed that the glucocorticoid (10(-8) M dexamethasone; dex) effect on BSP mRNA involves both direct and indirect pathways. To determine the molecular basis of the direct pathway on transcriptional regulation of the BSP we have isolated and characterized the promoter regions of both the human and rat BSP genes. The promoters are characterized by a highly conserved region (BSP box) encompassing the immediate promoter region, which includes a unique inverted TATA box overlapped by a putative (DR3) vitamin D3 response element (VDRE). Possible glucocorticoid response elements are present approximately 1 kb and approximately 1.4 kb further upstream. Transient transfection analysis of chimeric constructs linked to a luciferase reporter gene have shown Dex-stimulated expression in constructs that include one or both GREs, whereas vit D3 suppresses expression in a short construct that includes the VDRE.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodek
J
J
Medical Research Council Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, ONT, Canada.
Kim
R H
RH
Ogata
Y
Y
Li
J
J
Yamauchi
M
M
Zhang
Q
Q
Freedman
L P
LP
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002762:Cholecalciferol / Q000235:genetics / Q000494:pharmacology; D003739:Dental Cementum / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D015756:Genes, tat / Q000187:drug effects / Q000235:genetics; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism; D009805:Odontogenesis / Q000187:drug effects / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics; D012795:Sialoglycoproteins / Q000187:drug effects* / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
C546871:IBSP protein, human; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011965:Receptors, Glucocorticoid; D012795:Sialoglycoproteins; D002762:Cholecalciferol; D003907:Dexamethasone