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. 2018 Dec 14;38(6):BSR20181708.
doi: 10.1042/BSR20181708. Print 2018 Dec 21.

Osteogenic protein-1 attenuates nucleus pulposus cell apoptosis through activating the PI3K/Akt/mTOR pathway in a hyperosmotic culture

Yan Yang  1   2 , Xiyang Wang  3   2 , Zheng Liu  1   2 , Xiao Xiao  1   2 , Wenkai Hu  1   2 , Zhicheng Sun  1   2
Affiliations

Osteogenic protein-1 attenuates nucleus pulposus cell apoptosis through activating the PI3K/Akt/mTOR pathway in a hyperosmotic culture

Yan Yang et al. Biosci Rep. .

Retraction in

Abstract

Background: Previous studies have indicated that osteogenic protein-1 has protective effects on the biological functions of intervertebral disc cells. Hyperosmolarity is an important physicochemical factor within the disc nucleus pulposus (NP) region, which obviously promotes NP cell apoptosis.

Objective: To study the effects of osteogenic protein-1 (OP-1) on NP cell apoptosis induced by hyperosmolarity and the potential signaling transduction pathway.

Methods: Rat NP cells were cultured in a hyperosmotic medium with or without OP-1 addition for 7 days. Inhibitor 294002 and inhibitor FK-506 were used to investigate the role of the PI3K/Akt/mTOR pathway in this process. NP cell apoptosis were evaluated by cell apoptosis ratio, activity of caspase-3/9 and gene/protein expression of apoptosis-related molecules (Bax, Bcl-2, caspase-3/cleaved caspase-3 and cleaved PARP).

Results: OP-1 addition obviously decreased cell apoptosis ratio and caspase-3/9 activity, down-regulated gene/protein expression of pro-apoptosis molecules (Bax, caspase-3/cleaved casepase-3 and cleaved PARP), up-regulated gene/protein expression of anti-apoptosis molecule (Bcl-2) in a hyperosmotic culture. Moreover, OP-1 addition significantly increased protein expression of p-Akt and p-mTOR. Further analysis showed that addition of LY294002 and FK-506 partly attenuated these protective effects of OP-1 against NP cell apoptosis and activation of the PI3K/Akt/mTOR pathway in a hyperosmotic culture.

Conclusion: OP-1 can attenuate NP cell apoptosis through activating the PI3K/Akt/mTOR pathway in a hyperosmotic culture. The present study sheds a new light on the protective role of OP-1 in regulating disc cell biology and provides some theoretical basis for the application of OP-1 in retarding/regenerating disc degeneration.

Keywords: PI3K/Akt/mTOR; cell apoptosis; intervertebral disc degeneration; nucleus pulposus; osteogenic protein-1.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Nucleus pulposus (NP) cell apoptosis was measured by flow cytometry
Data are showed as mean ± SD, n=3. ‘HypOsm’ means a hyperosmolatic culture; ‘Inhs’ means addition of inhibitor LY294002 and inhibitor FK-506. * indicates a significant difference (P<0.05).
Figure 2
Figure 2. Analysis of caspase-3 activity and caspase-9 activity
Data are showed as mean ± SD, n=3. ‘HypOsm’ means a hyperosmolatic culture; ‘Inhs’ means addition of inhibitor LY294002 and inhibitor FK-506. * indicates a significant difference (P<0.05).
Figure 3
Figure 3. Gene expression of apoptosis-related molecules (Bcl-2, Bax and caspase-3) in nucleus pulposus (NP) cells in a hyperosmotic culture
Data are showed as mean ± SD, n=3. ‘HypOsm’ means a hyperosmolatic culture; ‘Inhs’ means addition of inhibitor LY294002 and inhibitor FK-506. * indicates a significant difference (P<0.05).
Figure 4
Figure 4. Protein expression of apoptosis markers (cleaved caspase-3 and cleaved PARP) in nucleus pulposus (NP) cells in a hyperosmotic culture
Data are showed as mean ± SD, n=3. ‘HypOsm’ means a hyperosmolatic culture; ’Inhs’ means addition of inhibitor LY294002 and inhibitor FK-506. * indicates a significant difference (P<0.05).
Figure 5
Figure 5. Activation of the PI3K/Akt/mTOR pathway in nucleus pulposus (NP) cells in a hyperosmotic culture
Data are showed as mean ± SD, n=3. ‘HypOsm’ means a hyperosmolatic culture; ‘Inhs’ means addition of inhibitor LY294002 and inhibitor FK-506. * indicates a significant difference (P<0.05).
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References

    1. Steffens D., Maher C.G., Pereira L.S., Stevens M.L., Oliveira V.C., Chapple M.. et al. (2016) Prevention of low back pain: a systematic review and meta-analysis. JAMA Intern. Med. 176, 199–208 10.1001/jamainternmed.2015.7431 - DOI - PubMed
    1. Hoy D., Bain C., Williams G., March L., Brooks P., Blyth F.. et al. (2012) A systematic review of the global prevalence of low back pain. Arthritis Rheum. 64, 2028–2037 10.1002/art.34347 - DOI - PubMed
    1. Wang X., Wang B., Zou M., Li J., Lu G., Zhang Q.. et al. (2018) CircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 3754–3768 10.1016/j.bbadis.2018.08.033 - DOI - PubMed
    1. Chen T., Cheng X., Wang J., Feng X. and Zhang L. (2018) Time-course investigation of intervertebral disc degeneration induced by different sizes of needle punctures in rat tail disc. Med. Sci. Monit. 24, 6456–6465 10.12659/MSM.910636 - DOI - PMC - PubMed
    1. Wang X., Zou M., Li J., Wang B., Zhang Q., Liu F.. et al. (2018) LncRNA H19 targets miR-22 to modulate H2 O2 -induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling. J. Cell. Biochem. 119, 4990–5002 10.1002/jcb.26738 - DOI - PubMed

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