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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
Summary
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.
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