Cell-penetrating superoxide dismutase attenuates oxidative stress-induced senescence by regulating the p53-p21(Cip1) pathway and restores osteoblastic differentiation in human dental pulp stem cells

细胞穿透性超氧化物歧化酶通过调节 p53-p21(Cip1)通路减轻氧化应激诱导的衰老并恢复人类牙髓干细胞的成骨细胞分化

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作者:Yoon Jung Choi, Jue Yeon Lee, Chong Pyoung Chung, Yoon Jeong Park

Background

Human dental pulp stem cells (DPSCs) have potential applications in tissue regeneration because of their convenient cell harvesting procedures and multipotent capacity. However, the tissue regenerative potential of DPSCs is known to be negatively regulated by aging in long-term culture and under oxidative stress. With an

Conclusion

Overall, cell-penetrating LMWP-SOD1 conjugates are effective for attenuation of cellular senescence and reversal of osteoblastic differentiation of DPSCs caused by oxidative stress inhibition. This result suggests potential application in the field of antiaging and tissue engineering to overcome the limitations of senescent stem cells.

Results

LMWP-SOD1 significantly attenuated enlarged and flattened cell morphology and increased senescence-associated β-galactosidase activity. Under the same conditions, LMWP-SOD1 abolished activation of the cell cycle regulator proteins, p53 and p21(Cip1), induced by hydrogen peroxide. In addition, LMWP-SOD1 reversed the inhibition of osteoblastic differentiation and downregulation of osteogenic gene markers induced by hydrogen peroxide. However, LMWP-SOD1 could not reverse the decrease in odontogenesis caused by hydrogen peroxide.

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