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Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice
Published on: September 16, 2020
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.
Abstract:
MicroRNA-21 (miR-21) contributes to anti-apoptosis in bone marrow mesenchymal stem cells (BMSC), but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible effect of miR-21 on regulating BMSCs directional migration and the expression of MMP-2/MMP-9 in BMSCs in vitro. BMSCs were successfully infected with miR-21-up lentivirus. Cell migration using Transwell assay indicated that upregulated expression of miR-21 could significantly promote BMSCs migration. Western blot analysis indicated that miR-21 significantly upregulated the expression of MMP-2 and MMP-9, which were related to metastasis-associated genes. GM6001, the specific MMPs inhibitor, abrogated the upregulated expression of MMP-2/MMP-9 and abolished the positive effect of miR-21 on promoting BMSCs migration. Meanwhile, miR-21 significantly enhanced Akt phosphorylation, as measured by Western blot analysis. LY294002, an inhibitor of Akt activation, abrogated the phosphorylation of Akt and abolished the positive effect of miR-21 on promoting BMSCs migration and upregulating MMP-2/MMP-9 expression. These results suggest that miR-21 contributes to BMSCs migration by upregulating MMP-2/MMP-9, potentially via the PI3K/Akt pathway.
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.

