Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1603
Peer-review started: April 3, 2020
First decision: August 9, 2020
Revised: August 30, 2020
Accepted: September 22, 2020
Article in press: September 22, 2020
Published online: December 26, 2020
Nucleus pulposus-derived mesenchymal stem cells (NPMSCs) can better tolerate the harsh acidic and hyperosmolar microenvironment of degenerative intervertebral discs (IVDs) than other types of mesenchymal stem cells (MSCs). NPMSCs can differentiate into nucleus pulposus cells and play an endogenous repair role in damaged IVDs.
To date, there has been no effective treatment for intervertebral disc degeneration (IDD). Overexpression of reactive oxygen species (ROS) causes apoptosis and senescence of NPMSCs, which eventually impairs their endogenous repair abilities. Thus, this study focuses on the strategies of how to protect NPMSCs from oxidative injury.
The present study investigated whether 6-gingerol (6-GIN) could protect NPMSCs from apoptosis induced by oxidative stress and the potential mechanism.
The protective effects of 6-GIN against hydrogen peroxide-induced injury in NPMSCs were investigated by analyzing the expression of apoptosis-associated proteins, matrix metalloproteinase (MMP), Annexin V-FITC/PI flow cytometry, and TUNEL assay. Additionally, autophagy-related tests including the protein, TEM, LC-3 immunofluorescence, and PI3K/Akt signaling pathway-related proteins were evaluated. The expression of extracellular matrix (ECM) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunofluorescence.
6-GIN could increase Bcl-2 expression and decrease Bax and caspase-3 expression. The MMP, Annexin V-FITC/PI flow cytometry, and TUNEL assay results further confirmed that 6-GIN treatment significantly inhibited NPMSC apoptosis induced by hydrogen peroxide. 6-GIN treatment promoted ECM expression by reducing the oxidative stress injury-induced increase in MMP-13 expression. Also, 6-GIN activated autophagy by increasing the expression of autophagy-related markers (Beclin-1 and LC-3) and decreasing the expression of p62.
6-GIN inhibits NPMSC apoptosis and ECM degeneration. Autophagy and the PI3K/Akt pathway are involved in this process.
We demonstrated the positive roles of 6-GIN in attenuating hydrogen peroxide-induced NPMSC apoptosis and protecting the ECM from degeneration. 6-GIN may be successfully applied to IDD therapy.