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FEBS Lett ; 590(3): 396-407, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26785690

ABSTRACT

miRNAs play a number of roles in bone, including mediating the pathological effects of inflammation. Here, we found that miR-33a-5p expression was significantly increased after TNF-α treatment during BMP-2-induced osteogenic differentiation of hBMSCs. Luciferase reporter assays and western blotting demonstrated that special AT-rich sequence-binding protein 2 (SATB2) is a target of miR-33a-5p. Moreover, we show that BMP-2 induces SATB2 expression by interacting with SATB2 directly via the BMP-2-RUNX2 pathway. However, TNF-α first decreases SATB2 expression by inhibiting miR-33a-5p degradation. We thus conclude that miR-33a-5p plays a central role in this complex regulatory network. These findings will help to understand the regulatory role of miR-33a-5p in the inflammatory process.


Subject(s)
Bone Morphogenetic Protein 2/metabolism , Matrix Attachment Region Binding Proteins/metabolism , MicroRNAs/metabolism , Osteogenesis , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Apoptosis , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 2/genetics , Cell Proliferation , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/agonists , Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors , Core Binding Factor Alpha 1 Subunit/metabolism , Female , Gene Expression Regulation, Developmental , Genes, Reporter , Humans , Male , Matrix Attachment Region Binding Proteins/agonists , Matrix Attachment Region Binding Proteins/antagonists & inhibitors , Matrix Attachment Region Binding Proteins/genetics , Mice , MicroRNAs/antagonists & inhibitors , Recombinant Proteins/metabolism , Signal Transduction , Stromal Cells/cytology , Stromal Cells/metabolism , Transcription Factors/agonists , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics
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