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

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.