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Microarray analysis of 1,25(OH)2D3 regulated gene expression in human primary osteoblasts

✍ Scribed by Paola Tarroni; Isabella Villa; Emanuela Mrak; Francesca Zolezzi; Michela Mattioli; Claudio Gattuso; Alessandro Rubinacci


Publisher
John Wiley and Sons
Year
2012
Tongue
English
Weight
448 KB
Volume
113
Category
Article
ISSN
0730-2312

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✦ Synopsis


Though extensive studies have been conducted, questions regarding the molecular effectors and pathways underlying the regulatory role of 1,25(OH) 2 D 3 in human osteoblasts other than cell differentiation and matrix protein production remain unanswered. This study aims to identify genes and pathways that are modulated by 1,25(OH) 2 D 3 treatment in human osteoblasts. Primary osteoblast cultures obtained from human bone tissue samples were treated with 1,25(OH) 2 D 3 (10 Γ€7 M) for 24 h and their transcritptomes were profiled by microarray analysis using the Affymetrix GeneChip 1 . Statistical analysis was conducted to identify genes whose expression is significantly modulated following 1,25(OH) 2 D 3 treatment. One hundred and fifty-eight genes were found to be differentially expressed. Of these, 136 were upregulated, indicating clear transcriptional activation by 1,25(OH) 2 D 3 . Biostatistical evaluation of microarray data by Ingenuity Pathways Analysis (IPA) revealed a relevant modulation of genes involved in vitamin D metabolism (CYP24), immune functions (CD14), neurotransmitter transporters (SLC1A1, SLC22A3), and coagulation [thrombomodulin (THBD), tissue plasminogen activator (PLAT), endothelial protein C receptor (PROCR), thrombin receptor (F2R)]. We identified a restricted number of highly regulated genes and confirmed their differential expression by real-time quantitative PCR (RT qPCR). The present genome-wide microarray analysis on 1,25(OH) 2 D 3 -treated human osteoblasts reveals an interplay of critical regulatory and metabolic pathways and supports the hypothesis that 1,25(OH) 2 D 3 can modulate the coagulation process through osteoblasts, activates osteoclastogenesis through inflammation signaling, modulates the effects of monoamines by affecting their reuptake. J.


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