miR-33a-5p modulates TNF-α-inhibited osteogenic differentiation by targeting SATB2 expression in hBMSCs

FEBS Lett. 2016 Feb;590(3):396-407. doi: 10.1002/1873-3468.12064. Epub 2016 Feb 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • 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
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Osteogenesis*
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • Transcription Factors / agonists
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • MIRN33a microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • RUNX2 protein, human
  • Recombinant Proteins
  • SATB2 protein, human
  • TNF protein, human
  • Transcription Factors
  • Tumor Necrosis Factor-alpha