Cerium oxide nanoparticles promote proliferation of primary osteoblasts via cell cycle machinery in vitro

Abstract

Nano cerium oxide, as a kind of rare earth oxide of the lanthanide series, had many potential applications in biomedical fields, such as drug carrier, antitumor, anti-oxidative damage, and biological imaging. Furthermore, cerium dioxide (CeO2) had anti-apoptotic effects on macrophages, cardiomyocytes, and pancreatic islets cells and relieved the symptom of autoimmune encephalomyelitis. CeO2 could also protect endothelial cells from oxidative injury. Previous research showed that CeO2 nanoparticles tended to accumulate in the bone (20% of the total intake) after intravenous administration. Moreover, our previous studies also showed that CeO2 nanoparticles could promote the proliferation, differentiation, and mineralization of osteoblasts (OBs). However, the mechanisms of it were still unclear. In the current study, we studied the effect and mechanisms of CeO2 nanoparticles on OBs. The cell proliferation, cellular uptake, endocytosis mechanism, cell cycle, BrdU incorporation, and cell adhesion forces were analyzed. The results showed that CeO2 nanoparticles entered the cell through caveolae and clathrin pathways and promoted the proliferation of primary OBs. The mechanism was that CeO2 nanoparticles pushed more OBs through the G1/S checkpoint and into S phase. Moreover, they also increased cell adhesion force. All in all, the results should be significant for the applications of nano CeO2 in biomedical fields and bone metabolism disease.

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Acknowledgments

We are grateful to Medical Comprehensive Experimental Center of Hebei University for the animal experiment.

Funding

This work was supported by the National Natural Science Foundation of China (21001038, 21471044), the Natural Science Foundation of Hebei Province (B2018201185, B2018201157, B2020201020), the Third Batch of Top Youth Talent Support Program of Hebei Province, the Priority Strategy Project of Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education (ts2019006), the Post-graduate’s Innovation Fund Project of Hebei University (hbu2019ss015), Science and Technology Project of Hebei Education Department (ZD2018036, ZD2020150), Medical Science Foundation of Hebei University (2020A03, 2020A04), Advanced Talents Incubation Program of the Hebei University (801260201020), and Talent Training Program of Hebei University (521000981169, 521000981196).

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Correspondence to Enjun Wang or Huifang Liu or Guoqiang Zhou.

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Wang, F., Wang, E., Han, J. et al. Cerium oxide nanoparticles promote proliferation of primary osteoblasts via cell cycle machinery in vitro. J Nanopart Res 23, 30 (2021). https://doi.org/10.1007/s11051-020-05115-y

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Keywords

  • Cerium oxide
  • Nanoparticles
  • Primary osteoblasts
  • Proliferation
  • Cell cycle
  • Biomedicine
  • Health effects