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Updated: Jan 9, 2026

Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
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H3K27 Acetylation-driven IGF2BP2 Mutates during the Aging of MSCs, thereby Influencing Osteogenic Differentiation and

Zimo Zhou1, Kai Kang2, Heran Wang1

  • 1Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

International Journal of Biological Sciences
|December 9, 2025
PubMed

Insights

Epigenetic changes in mesenchymal stem cells (MSCs) drive bone aging. Targeting the H3K27ac-IGF2BP2-HMGA1 pathway with CWI1-2 may treat osteoporosis.

Area of Science:

  • Epigenetics
  • Stem Cell Biology
  • Gerontology

Background:

  • Aging-related bone loss is linked to mesenchymal stem cell (MSC) senescence.
  • The precise epigenetic mechanisms governing MSC aging are not fully understood.

Purpose of the Study:

  • To investigate the role of histone H3 lysine 27 acetylation (H3K27ac) and IGF2BP2 in MSC aging.
  • To explore the potential of targeting this pathway for therapeutic intervention in age-related bone loss.

Main Methods:

  • Integrated ChIP-seq and RNA-seq analyses in aged murine bone marrow-MSCs (BM-MSCs).
  • Functional studies involving IGF2BP2 knockdown and overexpression.
  • Assessment of a key IGF2BP2 mutation (H65Q) and its effect on HMGA1.
  • Pharmacological inhibition of IGF2BP2 using CWI1-2 in vitro and in aged mice models.

Main Results:

  • Aged BM-MSCs showed diminished H3K27ac levels and reduced IGF2BP2 expression.
  • IGF2BP2 modulation affected senescence phenotypes; its H65Q mutation accelerated senescence via the HMGA1/p53/p21 pathway.
  • CWI1-2 treatment alleviated MSC senescence and improved bone regeneration in aged mice.

Conclusions:

  • The H3K27ac-IGF2BP2-HMGA1 axis is a key regulator of bone aging.
  • Pharmacological inhibition of IGF2BP2 with CWI1-2 shows therapeutic potential for age-related osteoporosis.
Keywords:
H3K27acIGF2BP2MSC senescencebone agingmutationosteogenic differentiation

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