Chondrocytes-derived exosomal miR-8485 regulated the Wnt/β-catenin pathways to promote chondrogenic differentiation of BMSCs

Biochem Biophys Res Commun. 2020 Mar 5;523(2):506-513. doi: 10.1016/j.bbrc.2019.12.065. Epub 2019 Dec 30.

Abstract

In indirect co-culture system, chondrocytes can induce differentiation of bone marrow mesenchymal stem cells (BMSCs) to chondrocytes without additional inducer. The participation of microRNAs (miRNAs) may take part in the chondrogenic differentiation. Present study aimed to investigate the effect and mechanism of chondrocytes-derived exosomal miRNA in BMSCs chondrogenic differentiation. Our data showed that miR-8485 was the exosomal miRNA derived from chondrocytes and transmitted to BMSCs. Functionally, miR-8485 silence in chondrocytes impaired exosome-induced chondrogenic differentiation of BMSCs. Mechanistically, exosomal miR-8485 targeted GSK3B to repress GSK-3β expression and targeted DACT1 to induce p-GSK-3β (Ser9), activating Wnt/β-catenin pathways. Our study firstly showed that chondrocytes-derived exosomal miR-8485 regulated the Wnt/β-catenin pathways to promote chondrogenic differentiation of BMSCs, providing innovative thoughts for cartilage reconstruction.

Keywords: BMSC; Chondrogenic differentiation; GSK-3β; Wnt/β-catenin pathways; miR-8485.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Chondrocytes / cytology*
  • Chondrogenesis / drug effects
  • Chondrogenesis / genetics
  • Exosomes / genetics*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / isolation & purification
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation / drug effects
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CTNNB1 protein, human
  • DACT1 protein, human
  • MIRN8485 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta