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

Abstract

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. 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. 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. 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. 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.