Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 126, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.msec.2021.112145
Keywords
CeONPs; Radiation; Mesenchymal stem cells; DNA damage; Osteogenesis; p53; Senescence
Categories
Funding
- National Science Foundation (NSF) Major Research Instrumentation (MRI) Program [ECCS:1726636]
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Supplementation of CeO nanoparticles at low concentration reduced cell senescence, enhanced cell autophagy, osteogenesis, and bone deposition, while high concentration led to an increase in p53 expression. CeO nanoparticles offer a multifunctional and protective effect against IR-induced cellular damage, as well as promoting osteogenic differentiation and new bone deposition.
Increased bone loss and risk of fracture are two of the main challenges for cancer patients who undergo ionizing radiation (IR) therapy. This decline in bone quality is in part, caused by the excessive and sustained release of reactive oxygen species (ROS). Cerium oxide nanoparticles (CeONPs) have proven antioxidant and regenerative properties and the purpose of this study was to investigate the effect of CeONPs in reducing IR-induced functional damage in human bone marrow-derived mesenchymal stromal cells (hBMSCs). hBMSCs were supplemented with CeONPs at a concentration of either 1 or 10 mu g/mL 24 h prior to exposure to a single 7 Gy irradiation dose. ROS levels, cellular proliferation, morphology, senescence, DNA damage, p53 expression and autophagy were evaluated as well as alkaline phosphatase, osteogenic protein gene expression and bone matrix deposition following osteogenic differentiation. Results showed that supplementation of CeONPs at a concentration of 1 mu g/mL reduced cell senescence and significantly augmented cell autophagy (p = 0.01), osteogenesis and bone matrix deposition 0.05) while increasing autophagy 3.5-fold and bone matrix deposition 5-fold (p = 0.0001 in both groups). When supplemented with 10 mu g/mL, p53 expression increased 3.5-fold (p < 0.05). We conclude that cellular uptake of CeONPs offered a significant, multifunctional and protective effect against IR-induced cellular damage while also augmenting osteogenic differentiation and subsequent new bone deposition. The use of CeONPs holds promise as a novel multifunctional therapeutic strategy for irradiation-induced bone loss.
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