Heme Oxygenase-1-Mediated Autophagy Protects against Oxidative Damage in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells

Abstract

Although endogenous nucleus pulposus-derived mesenchymal stem cell- (NPMSC-) based regenerative medicine has provided promising repair strategy for intervertebral disc (IVD) degeneration, the hostile microenvironments in IVD, including oxidative stress, can negatively affect the survival and function of the NPMSCs and severely hinder the endogenous repair process. Therefore, it is of great importance to reveal the mechanisms of the endogenous repair failure caused by the adverse microenvironments in IVD. The aim of this study was to investigate the effect of oxidative stress on the rat NPMSCs and its underlying mechanism. Our results demonstrated that oxidative stress inhibited cell viability, induced apoptosis, and increased the production of reactive oxygen species (ROS) in NPMSCs. In addition, the results showed that the expression level of heme oxygenase-1 (HO-1) increased at an early stage but decreased at a late stage when NPMSCs were exposed to oxidative stress, and the oxidative damages of NPMSCs could be partially reversed by promoting the expression of HO-1. Further mechanistic analysis indicated that the protective effect of HO-1 against oxidative damage in NPMSCs was mediated by the activation of autophagy. Taken together, our study revealed that oxidative stress could inhibit cell viability, induce apoptosis, and increase ROS production in NPMSCs, and HO-1-mediated autophagy might act as a protective response to the oxidative damage. These findings might enhance our understanding on the mechanism of the endogenous repair failure during IVD degeneration and provide novel research direction for the endogenous repair of IVD degeneration.

Scientific literature landscape analysis of researches on oxidative stress in intervertebral disc degeneration in web of science

“…1456 authors, 352 organizations, and 30 countries contributed to this field. Table 2 showed the top author with the most publications was Wang K ( n = 17) from Tongji Medical College ( Yin et al, 2021 ), the second was Shao ZW ( n = 16) from Tongji Medical College ( Chen S. et al, 2020 ), followed by Wang XY ( n = 15) from The Second Affiliated Hospital of Wenzhou Medical University ( Hu S. et al, 2021 ), Yang C ( n = 12) from Tongji Medical College ( Song et al, 2021 ), Zhang Y ( n = 12) from Third Military Medical University ( Xu et al, 2021 ). Of the 352 organizations, Huazhong University of Science Technology, Shanghai Jiao Tong University, Wenzhou Medical University, Zhejiang University, and Sun Yat Sen University had contributed 31, 21, 20, 15, and 12 publications, respectively.…”

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

“…Previous studies have shown that autophagy played a protective role against the oxidative stress in degenerative NPCs [ 24 , 30 , 32 ]. In this research, a significantly different autophagy score between NPC/MSC samples and NPC samples was observed ( Figure 6(a) ).…”

“…The dysregulation of autophagy has been proved to associate with the development of several human diseases, including the IDD [ 21 , 23 ]. Previous studies have shown that the oxidative stress could be relieved by activating the autophagy in degenerative NPCs, thereby reducing the apoptosis and degradation of extracellular matrix [ 22 , 24 , 25 ]. Nevertheless, to our knowledge, few articles focus on the effects of MSCs on the alleviation of oxidative stress via regulating the autophagy in IDD.…”

Transcription factor EB mediates oxidative stress-induced intervertebral disc degeneration via the NF-κB signaling pathway

“…OS inhibits cell viability, induces apoptosis, and finally promotes IDD (14). To evaluate the effects of OS induced by H 2 O 2 in human NP cells, we examined the viability and apoptosis of NP cells that had been treated with several H 2 O 2 concentrations using CCK-8 assays and a flow cytometry analysis.…”