Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway

Sci Rep. 2016 Jun 9:6:27622. doi: 10.1038/srep27622.

Abstract

HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation*
  • Cells, Cultured
  • Fracture Healing
  • Genetic Markers / genetics
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteogenesis*
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Dkk1 protein, rat
  • Genetic Markers
  • HSP70 Heat-Shock Proteins
  • Hspa1a protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Sost protein, rat
  • beta Catenin