Bone morphogenetic protein-7 retards cell subculture-induced senescence of human nucleus pulposus cells through activating the PI3K/Akt pathway

骨形态发生蛋白-7通过激活PI3K / Akt通路延缓细胞传代培养引起的人髓核细胞衰老

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作者:Chen Gong, Wei Pan, Wei Hu, Liang Chen

Background

Allogeneic disc cell is the main cellular resource in tissue engineering (TE)-based strategy to retard disc degeneration. However, the accessible disc cells often exhibit senescent phenotype when they are subcultured in vitro Hence, alleviating senescence of human disc cells during cell subculture is important for TE-based strategy to regenerate degenerative disc tissue.

Conclusion

BMP-7 alleviates subculture-induced senescence of human disc NP cells through activating the PI3K/Akt pathway. The present study provides new knowledge on allogeneic disc NP cell-based TE strategy to regenerate degenerative human disc tissue.

Methods

NP cells from human disc tissue were subcultured in vitro for six passages. Exogenous BMP-7 was added along with the culture medium to investigate its effects on senescence of NP cells. The inhibitor LY294002 was used to investigate the role of the PI3K/Akt pathway.

Objective

The present study was aimed to investigate whether bone morphogenetic protein-7 (BMP-7) can alleviate subculture-induced senescence of human nucleus pulposus (NP) cells in vitro

Results

Compared with the human disc NP cells cultured in the baseline culture medium, addition of BMP-7 increased cell proliferation potency and telomerase activity, decreased senescence-associated β-galactosidase (SA-β-Gal) activity and G0/G1 phase fraction, and down-regulated the expression of p16 and p53. Moreover, these positive effects of BMP-7 against senescence of human disc NP cells coincided with activation of the PI3K/Akt pathway. Further analysis showed that inhibitor LY294002 partly inhibited these protective effects of BMP-7 against senescence of human disc NP cells.

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