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Updated: Apr 28, 2026
Author Spotlight: Advancements in iPSCs and Genetic Disease Research
Published on: October 20, 2023
miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation
Weimin Qiu1, Moustapha Kassem2
1Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology, Odense University Hospital, J.B. Winsløws Vej 25, 1, DK-5000 Odense C, Denmark.
Abstract:
Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC. We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary, miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low bone mass diseases, e.g. osteoporosis.
Insights
MicroRNA-141-3p negatively regulates human mesenchymal stem cell (hMSC) proliferation and osteoblast differentiation by targeting CDC25A. Targeting this microRNA may offer new therapies for low bone mass diseases like osteoporosis.
Area of Science:
- Stem cell biology
- Molecular and cellular biology
- Biochemistry
Background:
- Wnt signaling dictates human mesenchymal stem cell (hMSC) differentiation into osteoblasts or adipocytes.
- MicroRNAs (miRNAs) are key regulators of osteoblast biology.
- Understanding miRNA regulation by Wnt signaling in hMSCs is crucial for bone biology research.
Purpose of the Study:
- To investigate miRNAs regulated by Wnt signaling in hMSCs.
- To elucidate the role of miR-141-3p in hMSC proliferation and osteoblast differentiation.
- To identify the molecular targets of miR-141-3p.
Main Methods:
- Identification of Wnt-regulated miRNAs in hMSCs.
- Assessment of miR-141-3p's effects on hMSC proliferation and cell cycle.
- Analysis of osteoblast differentiation markers (alkaline phosphatase, gene expression, matrix formation).
- Bioinformatic analysis, Western blotting, and 3'UTR reporter assays to identify miR-141-3p targets.
- siRNA-mediated knockdown of target genes.
Main Results:
- miR-141-3p was identified as a Wnt target that inhibits Wnt signaling.
- miR-141-3p suppressed hMSC proliferation by arresting cells in the G1 phase.
- miR-141-3p impaired osteoblast differentiation, reducing alkaline phosphatase activity, gene expression, and mineralized matrix formation.
- Cell division cycle 25A (CDC25A) was confirmed as a direct target of miR-141-3p.
- Knockdown of CDC25A mimicked the inhibitory effects of miR-141-3p on hMSC proliferation and osteoblast differentiation.
Conclusions:
- miR-141-3p functions as a negative regulator of hMSC proliferation and osteoblast differentiation.
- CDC25A is a direct downstream target mediating the effects of miR-141-3p.
- Modulating miR-141-3p activity presents a potential therapeutic strategy for anabolic bone treatment in diseases like osteoporosis.
