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Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species
Yuan, K; Mei, JT; Shao, DD; Zhou, F; Qiao, H; Liang, YK; Li, K; Tang, TT
2020-01-05
Source PublicationINTERNATIONAL JOURNAL OF NANOMEDICINE
ISSN1178-2013
Pages6355
SubtypeArticle
AbstractBackground: Cerium oxide nanoparticles (CeO(2)NPs) are potent scavengers of cellular reactive oxygen species (ROS). Their antioxidant properties make CeO(2)NPs promising therapeutic agents for bone diseases and bone tissue engineering. However, the effects of CeO(2)NPs on intracellular ROS production in osteoclasts (OCs) are still unclear. Numerous studies have reported that intracellular ROS are essential for osteoclastogenesis. The aim of this study was to explore the effects of CeO(2)NPs on osteoclast differentiation and the potential underlying mechanisms. Methods: The bidirectional modulation of osteoclast differentiation by CeO(2)NPs was explored by different methods, such as fluorescence microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The cytotoxic and proapoptotic effects of CeO(2)NPs were detected by cell counting kit (CCK-8) assay, TdT-mediated dUTP nick-end labeling (TUNEL) assay, and flow cytometry. Results: The results of this study demonstrated that although CeO(2)NPs were capable of scavenging ROS in acellular environments, they facilitated the production of ROS in the acidic cellular environment during receptor activator of nuclear factor kappa-B ligand (RANKL)-dependent osteoclast differentiation of bone marrow-derived macrophages (BMMs). CeO(2)NPs at lower concentrations (4.0 mu g/mL to 8.0 mu g/mL) promoted osteoclast formation, as shown by increased expression of Nfatcl and C-Fos, F-actin ring formation and bone resorption. However, at higher concentrations (greater than 16.0 mu g/mL), CeO(2)NPs inhibited osteoclast differentiation and promoted apoptosis of BM,Ms by reducing Bcl2 expression and increasing the expression of cleaved caspase-3, which may be due to the overproduction of ROS. Conclusion: This study demonstrates that CeO(2)NPs facilitate osteoclast formation at lower concentrations while inhibiting osteoclastogenesis in vitro by inducing the apoptosis of BMMs at higher concentrations by modulating cellular ROS levels.
DOI10.2147/IJN.S257741
WOS KeywordMESENCHYMAL STEM-CELL ; NF-KAPPA-B ; VALENCE STATES ; ALPHA ; CANCER ; INHIBITION ; APOPTOSIS ; THERAPY ; BINDING ; KINASE
Language英语
WOS Research AreaScience & Technology - Other Topics ; Pharmacology & Pharmacy
PublisherDOVE MEDICAL PRESS LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.sic.ac.cn/handle/331005/28387
Collection中国科学院上海硅酸盐研究所
Recommended Citation
GB/T 7714
Yuan, K,Mei, JT,Shao, DD,et al. Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2020:6355.
APA Yuan, K.,Mei, JT.,Shao, DD.,Zhou, F.,Qiao, H.,...&Tang, TT.(2020).Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species.INTERNATIONAL JOURNAL OF NANOMEDICINE,6355.
MLA Yuan, K,et al."Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species".INTERNATIONAL JOURNAL OF NANOMEDICINE (2020):6355.
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