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METTL3 promotes osteogenesis by regulating N6-methyladenosine-dependent primary processing of hsa-miR-4526

Yidan Song1, Hongyu Gao1, Yihua Pan2

  • 1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.

Stem Cells (Dayton, Ohio)
|January 5, 2025
PubMed
Abstract

Insights

Methyltransferase like 3 (METTL3) promotes osteogenesis by regulating N6-methyladenosine (m6A) modification of pri-miRNAs, specifically hsa-miR-4526, which inhibits TUBB3 expression to enhance bone formation.

Area of Science:

  • Stem cell biology
  • Epigenetics
  • Bone biology

Background:

  • The role of N6-methyladenosine (m6A) modification in pri-miRNA maturation and osteogenesis is not fully understood.
  • Investigating the mechanism of methyltransferase like 3 (METTL3) in human adipose-derived stem cell (hASC) osteogenesis is crucial.

Purpose of the Study:

  • To elucidate the function and regulatory mechanism of pri-miRNA m6A modification by METTL3 in hASC osteogenesis.
  • To identify specific pri-miRNAs involved in this process.

Main Methods:

  • Methylated RNA immunoprecipitation sequencing (MeRIP-seq) to identify methylated pri-miRNAs.
  • Quantitative real-time polymerase chain reaction (qRT-PCR) and co-immunoprecipitation to confirm interactions.
  • Dual luciferase reporter assays and rescue experiments to validate regulatory pathways.

Main Results:

  • METTL3 was found to promote osteogenesis both in vivo and in vitro.
  • METTL3-mediated m6A modification of pri-miR4526/5190 promotes hsa-miR-4526 processing.
  • Hsa-miR-4526 promotes osteogenesis by inhibiting TUBB3 expression, which normally suppresses hASC osteogenesis.

Conclusions:

  • This study reveals a novel mechanism of pri-miRNA m6A modification regulating hASC osteogenesis via the METTL3/hsa-miR-4526/TUBB3 axis.
  • Presents a new strategy for bone defect repair by targeting this pathway.
Keywords:
adipose stem cellsbonedifferentiationepigeneticsosteoblast

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