CXCL13 promotes the effect of bone marrow mesenchymal stem cells (MSCs) on tendon-bone healing in rats and in C3HIOT1/2 cells

Int J Mol Sci. 2015 Jan 30;16(2):3178-87. doi: 10.3390/ijms16023178.

Abstract

Objectives: Mesenchymal stem cells (MSCs) are potential effective therapy for tissue repair and bone regeneration. In present study, the effects of CXC chemokine ligand-13 (CXCL13) were evaluated on tendon-bone healing of rats.

Methods: Tendon bone healing of the rat model was established and biomechanical testing was performed at 2, 4, 8 weeks after surgery. Murine mesenchymal cell line (C3HIOT1/2 cells) was cultured. The expression of miRNA-23a was detected by real-time PCR. The protein expression of ERK1/2, JNK and p38 was detected by western blotting. MiR-23a mimic and inhibitor were used to overexpress or silence the expression of miR-23a.

Results: MSCs significantly elevated the levels of ultimate load to failure, stiffness and stress in specimens of rats, the effects of which were enhanced by CXCL13. The expression of miR-23a was down-regulated and the protein of ERK1/2 level was up-regulated by CXCL13 treatment in both in vivo and in vitro experiments. ERK1/2 expression was elevated by overexpression of miR-23a and reduced by miR-23a inhibitor.

Conclusions: These findings revealed that CXCL13 promoted the tendon-bone healing in rats with MSCs treatment, and implied that the activation of ERK1/2 via miR-23a was involved in the process of MSCs treated bone regeneration.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation
  • Cell Line
  • Chemokine CXCL13 / metabolism*
  • Chemokine CXCL13 / pharmacology
  • Disease Models, Animal
  • Gene Expression
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • MicroRNAs / genetics
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • RNA Interference
  • Rats
  • Tendon Injuries / genetics
  • Tendon Injuries / metabolism
  • Tendon Injuries / therapy*
  • Wound Healing*

Substances

  • Chemokine CXCL13
  • MIRN23 microRNA, rat
  • MicroRNAs
  • Mitogen-Activated Protein Kinases