scholarly journals 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

2020 ◽  
Author(s):  
Liwen Luo ◽  
Xiuying Jian ◽  
Hui Sun ◽  
Jinghao Qin ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intervertebral Disc ◽  
Signaling Pathways ◽  
Disc Degeneration ◽  
Western Blotting ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Effects ◽  
Normal Cartilage ◽  
Cartilage Endplate ◽  
Autophagy Pathway

Abstract Background Nucleus pulposus cells (NPCs) apoptosis is an important factor in exacerbating intervertebral disc degeneration (IVDD) that can be effectively suppressed by exosomes. The aim of this study was to reaearch whether normal cartilage endplate stem cells (CESCs) derived exosomes (N-Exos) were more conducive to activation of autophagy and inhibition of NPCs apoptosis and IVDD than degenerated CESCs derived exosomes (D-Exos) or not. Methods Rat CESCs were isolated and identified, and the exosomes produced by normal CESCs and degenerated CESCs were extracted. The bioinformatics differences between normal CESCs derived exosomes (N-Exos) and degenerated CESCs derived exosome (D-Exos) were analyzed by mass spectrometry, heat map and KEGG enrichment analysis biology. The effects of N-Exos and D-Exos on the inhibition of NPCs apoptosis were examined by TUNEL staining, flow cytometry and western blotting. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, western blotting and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in vivo. Results CESCs in the cartilage endplate (CEP) could secrete a large amount of exosomes. N-Exos were more conducive to activation of autophagy than D-Exos. The apoptotic rate of NPCs was decreased obviously after treatment with N-Exos than after D-Exos treatment. N-Exos inhibited NPCs apoptosis or attenuated IVDD in a rat tail model by activating the AKT and autophagy signaling pathways. Conclusions It was the first to confirm that CEP could delay the progression of IVDD through exosomes secreted by normal CESCs. The therapeutic effects of N-Exos on inhibiting NPCs apoptosis and slowing IVDD progression was more effective than D-Exos by activating the PI3K/AKT/autophagy pathway, which explained the reason that the incidence of IVDD was increased after inflammation of the CEP.

scholarly journals Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Dong Wang ◽  
Xin He ◽  
Di Wang ◽  
Pandi Peng ◽  
Xiaolong Xu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Protective Effect ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Specific Effect ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Autophagy Pathway ◽  
Dose Dependent

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which causes an enormous socioeconomic burden. Previous studies demonstrated that the apoptosis of nucleus pulposus (NP) cells and the dyshomeostasis of extracellular matrix (ECM) contributed to the pathogenesis of IDD, and effective therapies were still lacking. Quercetin, a natural flavonoid possessing a specific effect of autophagy stimulation and SIRT1 activation, showed some protective effect on a series of degenerative diseases. Based on previous studies, we hypothesized that quercetin might have therapeutic effects on IDD by inhibiting the apoptosis of NP cells and dyshomeostasis of ECM via the SIRT1-autophagy pathway. In this study, we revealed that quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress. We also found that quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration. Moreover, SIRT1 enzymatic activity inhibitor EX-527, suppressed quercetin-induced autophagy and the protective effect on NP cells, indicating that quercetin protected NP cells against apoptosis and prevented ECM degeneration via SIRT1-autophagy pathway. In vivo, quercetin was also demonstrated to alleviate the progression of IDD in rats. Taken together, our results suggest that quercetin prevents IDD by promoting SIRT1-dependent autophagy, indicating one novel and effective therapeutic method for IDD.

scholarly journals Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration

2022 ◽  
Vol 9 ◽  
Author(s):  
Weishi Liang ◽  
Bo Han ◽  
Yong Hai ◽  
Duan Sun ◽  
Peng Yin
Keyword(s):  
Stem Cells ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Bone Repair ◽  
Fine Tuning ◽  
Regulatory Function ◽  
Cartilage Endplate ◽  
Bone Injury ◽  
And Cartilage

Exosomes are extracellular vesicles formed by various donor cells that regulate gene expression and cellular function in recipient cells. Exosomes derived from mesenchymal stem cells (MSC-Exos) perform the regulatory function of stem cells by transporting proteins, nucleic acids, and lipids. Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, and it is characterized by a decreased number of nucleus pulposus cells, extracellular matrix decomposition, aging of the annulus fibrosus, and cartilage endplate calcification. Besides, nutrient transport and structural repair of intervertebral discs depend on bone and cartilage and are closely related to the state of the bone. Trauma, disease and aging can all cause bone injury. However, there is a lack of effective drugs against IDD and bone injury. Recent MSC-Exos fine tuning has led to significant progress in the IDD treatment and bone repair and regeneration. In this review, we looked at the uniqueness of MSC-Exos, and the potential treatment mechanisms of MSC-Exos with respect to IDD, bone defects and injuries.

scholarly journals Exosomes Derived from Human Urine-Derived Stem Cells Inhibit Intervertebral Disc Degeneration by Ameliorating Endoplasmic Reticulum Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
HongFei Xiang ◽  
WeiLiang Su ◽  
XiaoLin Wu ◽  
WuJun Chen ◽  
WenBin Cong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Intervertebral Disc ◽  
Er Stress ◽  
Signaling Pathways ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Erk Signaling ◽  
Control Group ◽  
Qrt Pcr

Objective. This study is aimed at determining the effects of human urine-derived stem cell-derived exosomes (USCs-exos) on pressure-induced nucleus pulposus cell (NPC) apoptosis and intervertebral disc degeneration (IDD) and on the ERK and AKT signaling pathways. Methods. The NPCs were obtained from patients with herniated lumbar discs. Western blot analysis (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine endoplasmic reticulum (ER) stress levels of NPCs under stress. Human USCs were identified using an inverted microscope, three-line differentiation experiments, and flow cytometry. A transmission microscope, nanoparticle size analysis, and WB procedures were used to identify the extracted exosomes and observe NPC uptake. A control group, a 48 h group, and a USCs-exos group were established. The control group was untreated, and the 48 h group was pressure-trained for 48 h, while the USCs-exos group was pressure-trained for 48 h and treated with USCs-exos. WB, qRT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis were used to determine the ER stress levels in stress conditions and after exosomal treatment. The AKT and ERK pathways were partially detected. Magnetic Resonance Imaging (MRI) and computed tomography (CT) were used to evaluate cell degeneration while exosomal effects on the intervertebral disc (IVD) tissue were determined by hematoxylin and eosin (HE) staining, Safranin O-fast green staining, immunohistochemical staining (IHC), nuclear magnetic resonance (NMR), spectrometric detection, and total correlation spectroscopy (TOCSY). IVD metabolites were also identified and quantified. Results. After pressure culture, ER stress markers (GRP78 and C/EBP homologous protein (CHOP)) in the NPCs were significantly elevated with time ( p < 0.05 ). Human USCs are short and spindle-shaped. They can successfully undergo osteogenic, adipogenic, and chondrogenic differentiation. In this study, these stem cells were found to be positive for CD29, CD44, and CD73. The exosomes were centrally located with a diameter of 50-100 nm. CD63 and Tsg101 were highly expressed while the expression of Calnexin was suppressed. The exosomes can be ingested by NPCs. USCs-exos significantly improved ER stress responses and inhibited excessive activation of the unfolded protein response (UPR) as well as cell apoptosis and disc degeneration through the AKT and ERK signaling pathways ( p < 0.05 ). Conclusion. Through the AKT and ERK signaling pathways, USCs-exos significantly inhibit ER stress-induced cell apoptosis and IDD under pressure conditions. It is, therefore, a viable therapeutic strategy.

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