MicroRNA-214 inhibits the osteogenic differentiation of human osteoblasts through the direct regulation of baculoviral IAP repeat-containing 7

Exp Cell Res. 2017 Feb 15;351(2):157-162. doi: 10.1016/j.yexcr.2017.01.006. Epub 2017 Jan 18.

Abstract

Osteoblasts and osteoclasts coordinate to monitor the dynamic osteogenic balance between bone formation and bone resorption. Hence, an investigation of the regulatory mechanisms underlying osteogenic osteoblast differentiation will provide more methods for bone repair and bone regeneration. In the present study, human osteoblast hFOB 1.19 cells were cultured. MicroRNA-214 (miR-214) expression significantly down-regulated during the osteogenic differentiation of hFOB 1.19 cells. In addition, miR-214 overexpression by miR-214 precursor transfection markedly inhibited the expression of alkaline phosphatase (ALP), collagen type I α1 (col1α1) and runt-related transcription factor 2 (Runx2), which concomitantly decreased ALP activity and the number of mineralized nodules but promoted the expression of signal transducer and activator of transcription 1 (STAT1), an osteogenesis blocker. We next found that miR-214 inhibited the expression of baculoviral IAP repeat-containing 7 (BIRC7), a member of the inhibitor of apoptosis proteins family. However, BIRC7 overexpression, which was induced by plasmid transfection, notably reversed the inhibitory effects of miR-214, indicating a potential BIRC7-dependent osteogenic differentiation manner mediated by miR-214. Taken together, our results demonstrate for the first time that miR-214 suppresses osteogenesis by targeting BIRC7, providing a possible therapeutic target for bone degenerative diseases.

Keywords: BIRC7; MiR-214; Osteoblasts; Osteogenic differentiation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Expression Regulation*
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis / genetics*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit
  • Inhibitor of Apoptosis Proteins
  • MIRN214 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RUNX2 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Luciferases
  • Alkaline Phosphatase