MicroRNA-21 promotes bone mesenchymal stem cells migration in vitro by activating PI3K/Akt/MMPs pathway

Chen Lv1, Shengwu Yang1, Xin Chen1

  • 1Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

Insights

MicroRNA-21 (miR-21) promotes bone marrow mesenchymal stem cell (BMSC) migration by increasing MMP-2/MMP-9 expression, likely through the PI3K/Akt pathway. This finding clarifies miR-21

Area of Science:

  • Stem cell biology
  • Molecular biology
  • Biochemistry

Background:

  • MicroRNA-21 (miR-21) is known to promote anti-apoptosis in bone marrow mesenchymal stem cells (BMSCs).
  • The specific role of miR-21 in regulating BMSC migration remains unclear.
  • Understanding miR-21's function in BMSC migration is crucial for regenerative medicine applications.

Purpose of the Study:

  • To investigate the effect of miR-21 on the directional migration of BMSCs.
  • To determine if miR-21 influences the expression of matrix metalloproteinases (MMP-2 and MMP-9) in BMSCs.
  • To elucidate the signaling pathway involved in miR-21-mediated BMSC migration.

Main Methods:

  • Lentiviral vectors were used to upregulate miR-21 expression in BMSCs.
  • Transwell assays were performed to assess cell migration.
  • Western blot analysis was employed to measure protein expression (MMP-2, MMP-9, phosphorylated Akt).
  • Specific inhibitors (GM6001 for MMPs, LY294002 for Akt) were used to validate the mechanisms.

Main Results:

  • Upregulation of miR-21 significantly enhanced BMSC migration.
  • miR-21 overexpression led to increased expression of MMP-2 and MMP-9.
  • Inhibition of MMPs or Akt activation abolished the pro-migratory effect of miR-21.
  • miR-21 was found to enhance Akt phosphorylation, suggesting involvement of the PI3K/Akt pathway.

Conclusions:

  • miR-21 promotes BMSC migration.
  • The pro-migratory effect of miR-21 is mediated through the upregulation of MMP-2 and MMP-9.
  • The PI3K/Akt signaling pathway plays a key role in miR-21-induced BMSC migration.