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  11. Dleu2/ezh2/gfi1 Axis Regulates The Proliferation And Apoptosis Of Human Bone Marrow Mesenchymal Stem Cells.

DLEU2/EZH2/GFI1 Axis Regulates the Proliferation and Apoptosis of Human Bone Marrow Mesenchymal Stem Cells.

Qing Yao1, Xuezhi He2, Jing Wang2

  • 1Department of Endocrinology and Metabolic Diseases, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213000, China.

Critical Reviews in Eukaryotic Gene Expression
|February 2, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Long non-coding RNA DLEU2 is downregulated in osteoporosis. Its knockdown inhibits human bone marrow mesenchymal stem cell proliferation and promotes apoptosis, revealing a potential therapeutic target for osteoporosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) are key regulators in osteoporosis pathogenesis.
  • Understanding the specific roles of lncRNAs in bone metabolism is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the function of lncRNA DLEU2 in the proliferation and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs).
  • To elucidate the molecular mechanism of DLEU2 in the context of osteoporosis (OP).

Main Methods:

  • High-throughput sequencing to identify differential lncRNAs in OP patients.
  • Transfection of hBMSCs with DLEU2 antisense oligonucleotides (ASO).
  • Assays for cell viability (MTT), proliferation (colony formation, EdU), cell cycle, apoptosis (flow cytometry), protein-RNA interactions (RIP, RNA pulldown), and protein-protein interactions (Co-IP).

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  • Chromatin immunoprecipitation (ChIP) and luciferase assays to confirm GFI1 binding to the DLEU2 promoter.

    • Main Results:

    • DLEU2 expression was significantly downregulated in bone tissues of OP patients.
    • Knockdown of DLEU2 inhibited hBMSC proliferation and induced apoptosis.
    • DLEU2 was found to interact with EZH2, leading to GFI1 activation.
    • GFI1 was confirmed to transcriptionally activate DLEU2, establishing a feedback loop.

    Conclusions:

    • The DLEU2/EZH2/GFI1 axis plays a critical role in suppressing proliferation and enhancing apoptosis of hBMSCs.
    • This regulatory axis represents a potential novel therapeutic strategy for treating osteoporosis.