Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression-Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress

Oxidative stress is relevant in compression-induced nucleus pulposus (NP) cell apoptosis and intervertebral disc (IVD) degeneration. Exosomes derived from bone mesenchymal stem cells (BMSCs-Exos) are key secretory products of MSCs, with important roles in tissue regeneration. This research is aimed at studying the protective impact of BMSCs-Exos on NP cell apoptosis caused by compression and investigating the underlying mechanisms. Our results indicated that we isolated BMSCs successfully. Exosomes were isolated from the BMSCs and found to alleviate the inhibitory effect that compression has on proliferation and viability in NP cells, decreasing the toxic effects of compression-induced NP cells. AnnexinV/PI double staining and TUNEL assays indicated that the BMSCs-Exos reduced compression-induced apoptosis. In addition, our research found that BMSCs-Exos suppressed compression-mediated NP oxidative stress by detecting the ROS and malondialdehyde level. Furthermore, BMSCs-Exos increased the mitochondrial membrane potential and alleviated compression-induced mitochondrial damage. These results indicate that BMSCs-Exos alleviate compression-mediated NP apoptosis by suppressing oxidative stress, which may provide a promising cell-free therapy for treating IVD degeneration.

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Mesenchymal stem cells deliver exogenous miR-21viaexosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.13316 ◽

2017 ◽

Vol 22 (1) ◽

pp. 261-276 ◽

Cited By ~ 68

Author(s):

Xiaofei Cheng ◽

Guoying Zhang ◽

Liang Zhang ◽

Ying Hu ◽

Kai Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Cell Apoptosis ◽

Intervertebral Disc Degeneration ◽

Nucleus Pulposus Cell

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The REDD1/TXNIP Complex Accelerates Oxidative Stress-Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/7397516 ◽

2021 ◽

Vol 2021 ◽

pp. 1-22

Author(s):

Huipeng Yin ◽

Kun Wang ◽

Abhirup Das ◽

Gaocai Li ◽

Yu Song ◽

...

Keyword(s):

Oxidative Stress ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Cell Apoptosis ◽

Redox Homeostasis ◽

Mitochondrial Pathway ◽

Nucleus Pulposus Cells ◽

Damage Response ◽

Induced Apoptosis ◽

Ivd Degeneration

The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.

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Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/4764071 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Yiqiang Hu ◽

Liang Huang ◽

Min Shen ◽

Yunlu Liu ◽

Guohui Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Cellular Therapy ◽

Adverse Outcomes ◽

Protective Effects ◽

Apoptosis Pathway ◽

Ivd Degeneration

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

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Hydroxysafflor yellow A attenuates oxidative stress injury‑induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.11105 ◽

2021 ◽

Vol 23 (2) ◽

Author(s):

Shuo Yang ◽

Wenbo Liao

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Cell Line ◽

Nucleus Pulposus ◽

Nucleus Pulposus Cell ◽

Hydroxysafflor Yellow A ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Induced Apoptosis

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Injectable Hydrogel Combined with Nucleus Pulposus-Derived Mesenchymal Stem Cells for the Treatment of Degenerative Intervertebral Disc in Rats

Stem Cells International ◽

10.1155/2019/8496025 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 5

Author(s):

Feng Wang ◽

Li-ping Nan ◽

Shi-feng Zhou ◽

Yang Liu ◽

Ze-yu Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Rat Model ◽

Injectable Hydrogel ◽

Cell Scaffold ◽

Ivd Degeneration

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83±227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.

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