miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/β-Catenin Signaling Pathway

DNA Cell Biol. 2017 Aug;36(8):715-724. doi: 10.1089/dna.2017.3657. Epub 2017 Jun 16.

Abstract

Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated. Calcium-rich deposit (mineralization) is also a typical osteogenic differentiation marker that could be visualized by alizarin red S (ARS) staining. Inhibiting miR-139-5p notably promotes the hBMSC osteoblast differentiation, which, however, will be reduced by overexpressed miR-139-5p. This result has been made based on the alternations of ALP activity, ARS staining, as well as expression of osteogenic genes, including runt-related gene-2 (Runx2), collagen I (Col-1), and osteocalcin (OCN). miR-139-5p exerts its role in BMSC osteogenesis most probably through the Wnt/β-catenin pathway, by direct targeting CTNNB1 and frizzled 4 (FZD4), essential factors of Wnt/β-catenin pathway. In conclusion, according to the present study, inhibiting miR-139-5p could be a promising strategy in hBMSC osteogenesis.

Keywords: CTNNB1; FZD4; Wnt/β-catenin; hBMSCs; miR-139-5p; osteogenesis.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Antigens, Differentiation
  • Calcification, Physiologic
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Collagen Type I / biosynthesis
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit / biosynthesis
  • Down-Regulation
  • Frizzled Receptors / metabolism
  • Gene Expression Regulation, Developmental*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Osteocalcin / biosynthesis
  • Osteogenesis / genetics*
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / metabolism

Substances

  • Antigens, Differentiation
  • CTNNB1 protein, human
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit
  • FZD4 protein, human
  • Frizzled Receptors
  • MIRN139 microRNA, human
  • MicroRNAs
  • RUNX2 protein, human
  • beta Catenin
  • Osteocalcin
  • Alkaline Phosphatase