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Osteoclasts drive bone formation in ectopic and orthotopic environments
Yang Zhang1, Taozhao Yu2, Qianfeng Xiang3
1School of Dentistry, Shenzhen University Medical School, Shenzhen, 518055, China; Regenerative Biomaterials, Department of Dentistry, Radboudumc, Nijmegen, 6525GA, the Netherlands.
Biomaterials
|May 4, 2025
Summary
Osteoclasts, not just bone resorbers, can stimulate new bone formation. Osteoclast-based constructs effectively promote bone regeneration and marrow formation, offering new therapeutic avenues for bone repair.
Area of Science:
- Cell Biology
- Orthopedics
- Regenerative Medicine
Background:
- Mesenchymal stromal cells (MSCs) have been the focus for bone formation therapies, but clinical results are unsatisfactory.
- Emerging evidence suggests osteoclasts play a key role in stimulating bone formation, preceding osteoblastic activity in bone remodeling.
Purpose of the Study:
- To investigate the role of osteoclasts in bone formation and regeneration.
- To evaluate osteoclast-based constructs for ectopic and orthotopic bone induction and regeneration.
Main Methods:
- Preparation of osteoclast-based constructs using primary mouse osteoclasts.
- Ectopic implantation to assess de novo bone and bone marrow formation.
- Orthotopic implantation in a mouse cranial defect model to evaluate bone regeneration.
Main Results:
- Osteoclast-based constructs demonstrated robust de novo bone formation, comparable to BMP-2 treatment.
- Significant de novo bone marrow formation was observed with osteoclast constructs (73%) and BMP-2 controls (91%).
- Osteoclast constructs significantly enhanced bone regeneration in a cranial defect model (2.5-fold increase vs. scaffold only).
Conclusions:
- Osteoclasts possess osteoinductive and osteogenic capacities, challenging traditional views of their function.
- Osteoclast-based cell constructs represent a promising new strategy for bone repair and regeneration.
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