SF1670 inhibits apoptosis and inflammation via the PTEN/Akt pathway and thus protects intervertebral disc degeneration

H.-Y. Fu, L. Shen, X.-S. Gao, D.-X. Cui, Z.-Y. Cui

Department of Rehabilitation Medicine, Affiliated Hospital of Weifang Medical University, Weifang, China. cuizhenyang1116@163.com

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• Orthopedics

OBJECTIVE: Intervertebral disc degeneration (IVDD) is associated with the apoptosis of nucleus pulposus (NP) cells. Previous studies have shown that PTEN plays crucial roles in cell survival and apoptosis. The effect of PTEN inhibitors on cell survival following IVDD has been rarely examined. In this study, we investigated the protective effect of SF1670, as a specific PTEN inhibitor, on an in vitro NP cells degenerated model.

PATIENTS AND METHODS: We collected human disc samples from IVDD patients and detected PTEN expression in them with different degenerated degrees. NP cells were isolated from the samples and exposed to IL-1β with or without SF1670. Then, cells viability was determined by CCK-8 assay. We also measured the levels of collagen II, p16, p53, PTEN, Akt, aggrecan, caspase 3/9, Bax, Bcl-2, and several inflammatory factors in NP cells.

RESULTS: We found that the expression of PTEN markedly increased in severely degenerated disc tissues. The data showed that IL-1β upregulated the expressions of p16, p53, PTEN, caspase 3/9, and Bax, but decreased the expressions of collagen II, Akt, aggrecan, and Bcl-2. Surprisingly, the treatment with SF1670 could significantly reverse the regulatory effects of IL-1β. Moreover, relative levels of IL-6, IL-8, TNF-α, and MMP3/9/13 were significantly suppressed by SF1670 stimuli compared with IL-1β group.

CONCLUSIONS: Overall, these results demonstrated that SF1670 prevented NP degradation via suppressing apoptosis and inflammation through inhibition of PTEN and activation of Akt. SF1670 may become a novel target for the therapy of IVDD in the future.

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