Skeletal Stem Cells Rescue Radiation-Induced Osteogenic Precursor Cell Dysfunction via the Wnt/β-Catenin Signaling Pathway
- Dose Response. 2026 Apr 7;24(2):15593258261440983. doi: 10.1177/15593258261440983.
- 1. Nuclear Emergency Medicine Department, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- 2. Clinical Diagnosis and Treatment Center of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- 3. Department of Orthopedic, Suzhou Xiangcheng People's Hospital, Suzhou, China.
- 4. Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin, China.
- 5. Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
- 6. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
Objective: Skeletal stem cells (SSCs), a specialized subset of mesenchymal stem cells, drive bone regeneration. This study aimed to characterize the pathological effects of ionizing radiation (IR) on osteogenic precursor cells (MC3T3-E1) and to elucidate the therapeutic efficacy and underlying molecular mechanisms of SSC-mediated rescue.
Methods: Experiments were performed using clonogenic assay, micronucleus assay, flow cytometry, osteogenic differentiation assessment, migration assay, and animal model establishment.
Results: The results demonstrated that IR compromised the clonogenic capacity of MC3T3-E1 cells, exacerbated genomic damage, induced Apoptosis, and significantly impaired their osteogenic differentiation and migratory potential. In vivo, IR led to deterioration of the skeletal microarchitecture,as evidenced by reduced bone mineral density (BMD), decreased bone volume fraction (BV/TV), and a concomitant increasee in marrow adiposity and osteoclastogenesis. Notably, SSC treatment significantly reversed these deleterious effects in both cellular and animal models. Mechanistically, SSC intervention upregulated key osteogenic regulators (RUNX22, COL1A1, and OCN) and stabilized β-catenin. Crucially, the radioprotective efficacy of SSCs was abrogated by the Wnt/β-catenin Inhibitor MSAB, demonstrating the pathway's indispensable role in the rescue process.
Conclusions: This study indicates that SSCs effectively alleviate IR-induced injury to osteoblast progenitor cells, providing compelling evidence and establishing a novel therapeutic paradigm for treating radiation-related skeletal complications.