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Dnmt3b ablation affects fracture repair process by regulating apoptosis

Xu Wang1,2, Qinwen Ge1,2, Qinghe Zeng1,2

  • 1Institute of Orthopedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China.

BMC Musculoskeletal Disorders
|February 27, 2024
PubMed
Abstract

Insights

Ablating DNA methyltransferase 3b (Dnmt3b) in Gli1-positive stem cells impairs fracture healing. This leads to reduced callus formation and poor bone remodeling by affecting chondrocyte maturation and apoptosis.

Area of Science:

  • Stem cell biology
  • Skeletal biology
  • Epigenetics

Background:

  • DNA methyltransferase 3b (Dnmt3b) is crucial for fracture repair.
  • Previous studies linked Dnmt3b to fracture healing in Prx1-positive stem cells and chondrocytes.
  • The role of Dnmt3b in Gli1-positive stem cells during fracture repair remains unexplored.

Purpose of the Study:

  • To investigate the impact of Dnmt3b ablation in Gli1-positive stem cells on fracture healing in mice.
  • To elucidate the underlying molecular mechanisms of Dnmt3b's role in fracture repair.

Main Methods:

  • Generation of Gli1-CreERT2; Dnmt3bflox/flox (Dnmt3bGli1ER) mice for tibia fracture studies.
  • Analysis of fracture callus tissues using X-ray, micro-CT, biomechanical testing, histopathology, and TUNEL assay.

Main Results:

  • Dnmt3b ablation in Gli1-positive stem cells significantly reduced cartilaginous callus formation.
  • Chondrogenic (Sox9) and osteogenic (Runx2) markers were decreased in Dnmt3bGli1ER mice.
  • Delayed bone callus remodeling, reduced biomechanical properties, and altered apoptosis markers (upregulated Caspase-3/8, BCL-2) were observed.

Conclusions:

  • Dnmt3b ablation in Gli1-positive stem cells negatively affects fracture healing.
  • This impairment is mediated by regulating apoptosis, leading to decreased chondrocyte hypertrophic maturation and poor fracture healing.
Keywords:
Dnmt3bFracture healingPeriosteum stem cells

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