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.
Keywords:
SATB2; TNF-α; hBMSCs; miR-33a-5p; osteogenesis.
© 2016 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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Bone Morphogenetic Protein 2 / genetics
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Bone Morphogenetic Protein 2 / metabolism*
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Cell Proliferation
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Cells, Cultured
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Core Binding Factor Alpha 1 Subunit / agonists
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Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors
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Core Binding Factor Alpha 1 Subunit / metabolism
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Female
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Gene Expression Regulation, Developmental
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Genes, Reporter
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Humans
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Male
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Matrix Attachment Region Binding Proteins / agonists
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Matrix Attachment Region Binding Proteins / antagonists & inhibitors
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Matrix Attachment Region Binding Proteins / genetics
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Matrix Attachment Region Binding Proteins / metabolism*
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Mice
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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Osteogenesis*
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Recombinant Proteins / metabolism
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Signal Transduction
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Stromal Cells / cytology
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Stromal Cells / metabolism
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Transcription Factors / agonists
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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BMP2 protein, human
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Bone Morphogenetic Protein 2
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Core Binding Factor Alpha 1 Subunit
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MIRN33a microRNA, human
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Matrix Attachment Region Binding Proteins
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MicroRNAs
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RUNX2 protein, human
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Recombinant Proteins
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SATB2 protein, human
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TNF protein, human
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Transcription Factors
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Tumor Necrosis Factor-alpha