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Updated: May 31, 2026
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Irradiator Commissioning and Dosimetry for Assessment of LQ α and β Parameters, Radiation Dosing Schema, and in vivo Dose Deposition
Published on: March 11, 2021
Insights Into Dose-Dependent Bone Toxicity Following Partial-Body Exposure to Fractionated Ionizing Radiation In Vivo
Fei Wei1, Sanjeda S Jennifer2, Mahmoud Omer1
1Biionix Cluster, College of Medicine, University of Central Florida, Orlando, Florida, USA.
Summary
Ionizing radiation (IR) causes bone toxicity through unknown mechanisms. This study reveals early cellular changes and molecular signatures, offering potential targets for preventing and treating radiation-induced bone injury.
Area of Science:
- Biomedical Sciences
- Radiation Oncology
- Cell Biology
Background:
- Ionizing radiation (IR) causes significant bone toxicity, leading to bone loss, fractures, and pain.
- The precise mechanisms underlying IR-induced bone toxicity are largely unknown, and effective countermeasures are lacking.
- Understanding these mechanisms and identifying biomarkers are crucial for developing diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the cellular and molecular responses to high-dose IR in bone cells and tissues.
- To compare the effects of IR on mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes in vitro.
- To assess the in vivo response of bone to cumulative IR doses and identify early micromechanisms of bone fragility.
Main Methods:
- In vitro studies on bone-derived mesenchymal stem cells, macrophages, osteoblasts, and osteocytes exposed to IR.
- In vivo assessment of bone response to cumulative IR doses (8, 16, 24 Gy).
- Analysis of DNA damage, apoptosis, reactive oxygen species, mineral deposition, intercellular communication, bone mechanical properties, and proteomic signatures.
Main Results:
- Osteoblast to osteocyte transition showed radioresistance to DNA damage, apoptosis, ROS formation, and impaired mineral deposition.
- IR stimulated the formation of tunneling nanotube-like structures in macrophages, a novel intercellular communication pathway.
- Bone fracture stress decreased significantly after a single 8 Gy exposure, preceding microarchitectural deterioration, suggesting early micromechanisms.
- Dose- and severity-related proteomic signatures of pathological toxicity were identified.
Conclusions:
- IR-induced bone toxicity involves complex cellular responses and novel intercellular communication mechanisms.
- Early micromechanisms contributing to bone fragility may originate in the bone's organic/material component.
- Identified molecular signatures and cellular processes provide potential targets for therapeutic interventions against IR-induced bone injury.
