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Published on: May 4, 2018
PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells
Bo Qu1, Xun Xia2, Hong-hua Wu2
1Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
Abstract:
Differentiation-specific microRNAs may play a critical role in MSC differentiation, and they can be altered by PDGF signaling. We propose that PDGF modulates MSC differentiation by regulating microRNA expression. Therefore, we investigated whether PDGF treatment could alter the expression profile of miRNAs in MSCs. Furthermore, we assessed the osteoblast phenotype of MSCs after inducing osteogenic differentiation. We found that PDGF treatment significantly inhibits the osteogenic differentiation of MSCs and that miR-138 gene transcription is controlled by PDGF signaling. Our results confirm that miR-138 inhibits the osteogenic differentiation of MSCs and suppresses the phosphorylation of FAK, ERK1/2, and Runx2. Furthermore, our study clearly demonstrates that downregulation of Runx2 by miR-138 is critical for the PDGF-mediated inhibition of osteogenic differentiation of MSCs. These findings indicate that inhibition of miR-138 function in MSCs, either by treatment with anti-miR-138 or by overexpression of the miR-138 target sequence (miRNA sponge), could represent a potential therapeutic strategy for the treatment of bone homeostasis disorders caused by activation of the PDGF pathway.
Insights
Platelet-derived growth factor (PDGF) inhibits mesenchymal stem cell (MSC) osteogenic differentiation by regulating microRNA-138 (miR-138). Inhibiting miR-138 may treat bone disorders.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are crucial regulators of cell differentiation.
- Platelet-derived growth factor (PDGF) signaling influences mesenchymal stem cell (MSC) behavior.
- The interplay between PDGF and miRNA expression in MSC differentiation is not fully understood.
Purpose of the Study:
- To investigate if PDGF alters miRNA expression profiles in MSCs.
- To determine the role of specific miRNAs in PDGF-modulated MSC osteogenic differentiation.
- To explore potential therapeutic strategies targeting miRNA pathways for bone homeostasis disorders.
Main Methods:
- MSCs were treated with PDGF.
- miRNA expression profiles were analyzed.
- Osteogenic differentiation was induced and assessed.
- Western blotting was used to evaluate protein phosphorylation (FAK, ERK1/2, Runx2).
- miR-138 mimics and inhibitors were employed.
Main Results:
- PDGF treatment significantly inhibited MSC osteogenic differentiation.
- PDGF signaling controls miR-138 gene transcription.
- miR-138 was found to inhibit osteogenic differentiation by suppressing FAK, ERK1/2, and Runx2 phosphorylation.
- Downregulation of Runx2 by miR-138 is critical for PDGF-mediated inhibition of osteogenic differentiation.
Conclusions:
- PDGF inhibits MSC osteogenic differentiation via miR-138 regulation.
- miR-138 acts as a negative regulator of osteogenic differentiation in MSCs.
- Targeting miR-138 (e.g., using anti-miR-138 or miRNA sponges) offers a potential therapeutic approach for bone homeostasis disorders linked to PDGF pathway activation.
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