Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway

Abstract

Objective Excessive apoptosis of nucleus pulposus cells (NPCs) induced by various stresses, including compression, contributes to the development of intervertebral disc degeneration (IVDD). Mesenchymal stem cells (MSCs) can benefit the regeneration of NPCs and delay IVDD, but the underlying molecular mechanism is poorly understood. This study aimed to evaluate the antiapoptosis effects of bone marrow-derived MSC (BMSC) on rat NPCs exposed to compression and investigate whether the mitochondrial pathway was involved. Methods BMSCs and NPCs were cocultured in the compression apparatus at 1.0 MPa for 36 h. Cell viability, apoptosis, mitochondrial function, and the expression of apoptosis-related proteins were evaluated. Results The results showed that coculturing with BMSCs increased the cell viability and reduced apoptosis of NPCs exposed to compression. Meanwhile, BMSCs could relieve the compression-induced mitochondrial damage of NPCs by decreasing reactive oxygen species level and maintaining mitochondrial membrane potential as well as mitochondrial integrity. Furthermore, coculturing with BMSCs suppressed the activated caspase-3 and activated caspase-9, decreased the expressions of cytosolic cytochrome c and Bax, and increased the expression of Bcl-2. Conclusions Our results suggest that BMSCs can protect against compression-induced apoptosis of NPCs by inhibiting the mitochondrial pathway and thus enhance our understanding on the MSC-based therapy for IVDD.

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

“…As shown in Figure A, the 1.0 MPa compression reduced the viability of human NP cells in a time‐dependent manner from 0 to 48 hours. Considering that compression treatment for 36 hours resulted in a 49% reduction in cell viability and that this time point of 36 hours has been used in several studies to induce oxidative stress, mitochondrial dysfunction and apoptosis in NP cells, we used this 36 hours time point in subsequent experiments. In addition, our results showed that MitoQ provided substantial protection against this compression‐induced reduction in cell viability (Figure B).…”

“…Therefore, the in vitro and ex vivo models of IDD induced by compression are more in line with the pathogenesis of IDD. Studies have reported that ROS overproduction, mitochondrial dysfunction and apoptosis were induced by compression at a magnitude of 1.0 MPa in NP cells, all of which were closely related to IDD . Thus, we for the first time systematically investigated the changes in mitochondrial dynamics, mitophagy and Nrf2 signalling in human NP cells under 1.0 MPa compression.…”

“…Considering that compression treatment for 36 hours resulted in a 49% reduction in cell viability and that this time point of 36 hours has been used in several studies to induce oxidative stress, mitochondrial dysfunction and apoptosis in NP cells, 10,11,45,46…”

“…Studies have reported that ROS overproduction, mitochondrial dysfunction and apoptosis were induced by compression at a magnitude of 1.0 MPa in NP cells, all of which were closely related to IDD. 10,11,45,46 Thus, we for the first time systematically investigated the changes in mitochondrial dynamics, mitophagy and Nrf2 signalling in human NP cells under 1.0 MPa compression. In addition, we studied the effect of MitoQ on human NP cells, as well as the roles of mitochondrial dynamics, mitophagy and Nrf2 signalling in the action of MitoQ.…”

Exosomes from normal cartilage endplate stem cells ameliorate intervertebral disc degeneration more effectively than exosomes from degenerated cartilage endplate stem cell by activating the AKT/autophagy pathway

“…Previous studies showed that there were a large number of progenitor cells that differentiated into osteoblasts, adipocytes and chondrocytes in human CEP tissues, and these progenitor cells were de ned as cartilage endplate stem cells (CESCs) [6]. It has been demonstrated that CESCs perform powerful functions in inhibiting IVDD by promoting NPCs regeneration and regulating the homeostasis of the intervertebral disc [7][8][9]. However, the detailed mechanism remains unclear.…”