Evidence of vitamin D and interferon-beta cross-talk in human osteoblasts with 1 alpha,25-dihydroxyvitamin D-3 being dominant over interferon-beta in stimulating mineralization

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It is well established that 1a-25-dihydroxyvitamin D3 (1,25D3) regulates osteoblast function and stimulates mineralization by human osteoblasts. The aim of this study was to identify processes underlying the 1,25D3 effects on mineralization. We started with gene expression profiling analyses of differentiating human pre-osteoblast treated with 1,25D3. Bioinformatic analyses showed interferon-related and -regulated genes (ISG) to be overrepresented in the set of 1,25D3-regulated genes. 1,25D3 down-regulated ISGs predominantly during the pre-mineralization period. This pointed to an interaction between the vitamin D and IFN signaling cascades in the regulation of osteoblast function. Separately, 1,25D3 enhances while IFN beta inhibits mineralization. Treatment of human osteoblasts with 1,25D3 and IFN beta showed that 1,25D3 completely overrules the IFN beta inhibition of mineralization. This was supported by analyses of extracellular matrix gene expression, showing a dominant effect of 1,25D3 over the inhibitory effect of IFN beta. We identified processes shared by IFN beta- and 1,25D3-mediated signaling by performing gene expression profiling during early osteoblast differentiation. Bioinformatic analyses revealed that genes being correlated or anti-correlated with interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) were associated with osteoblast proliferation. In conclusion, the current study demonstrates a cross talk between 1,25D3 and IFN beta in osteoblast differentiation and bone formation/mineralization. The interaction is complex and depends on the process but importantly, 1,25D3 stimulation of mineralization is dominant over the inhibitory effect of IFN beta. These observations are of potential clinical relevance considering the impact of the immune system on bone metabolism in conditions such as rheumatoid arthritis. J. Cell. Physiol. 227: 32583266, 2012. (C) 2011 Wiley Periodicals, Inc.
Original languageUndefined/Unknown
Pages (from-to)3258-3266
Number of pages9
JournalJournal of Cellular Physiology
Issue number9
Publication statusPublished - 2012

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