The expression of Fas ligand on normal and stabbed-disc cells in a rabbit model of intervertebral disc degeneration: a possible pathogenesis

2007 ◽  
Vol 6 (5) ◽  
pp. 425-430 ◽  
Author(s):  
Jing Wang ◽  
Tiansi Tang ◽  
Huilin Yang ◽  
Xiaoshen Yao ◽  
Liang Chen ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Fas Ligand ◽  
Rabbit Model ◽  
Nucleus Pulposus Cells ◽  
Physiological Barrier ◽  
Disc Cells ◽  
The Mean ◽  
Privileged Site

Object The nucleus pulposus has been reported to be an immunologically privileged site. The expression of Fas ligand (FasL) on normal and herniated lumbar disc cells has been reported. The relationship between a physiological barrier and the role of FasL has not yet been addressed. To clarify this relationship and to investigate a possible pathogenesis of intervertebral disc degeneration (IDD), the expression of Fas and FasL (a mean apoptosis index) on normal and stabbed-disc cells was examined in a rabbit model of IDD. Methods Using defined needle gauges and depths, the anular puncture model of IDD was established in rabbits. The normal and stabbed discs were harvested at 3, 6, and 10 weeks after surgery. Immunohistochemical staining of these discs for Fas and FasL was performed using standard procedures. The mean apoptosis indices of the disc cells were determined using flow cytometry analysis. The nucleus pulposus cells from the normal discs exhibited relatively weak immunopositivity, whereas the nucleus pulposus cells from the stabbed discs exhibited strong immunopositivity. There was a significant difference (p < 0.001) in the percentage of FasL-positive nucleus pulposus cells between the normal discs and the stabbed discs. The mean apoptosis indices of the stabbed-disc cells at 3, 6, and 10 weeks poststab were significantly higher than those in normal disc cells (p < 0.001, 0.002, and 0.006, respectively). There was a significant correlation between the degree of FasL-positive expression and the degree of Fas-positive expression of the nucleus pulposus cells poststab (r = 0.571, p = 0.0036). Conclusions These observations indicate that the nucleus pulposus is an immunologically privileged site. This immunological privilege is maintained by FasL and the physiological barrier together. When the physiological barrier was damaged (by stabbing the disc), the role of FasL changed, and FasL was coexpressed with Fas to induce apoptosis of disc cells. These results indicate that an autoimmune reaction may be a possible pathogenesis of IDD.

scholarly journals LncRNA GAS5 as miR-26a-5p Sponge Regulates the PTEN/PI3K/Akt Axis and Affects Extracellular Matrix Synthesis in Degenerative Nucleus Pulposus Cells in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Tan ◽  
Yifang Xie ◽  
Ye Yuan ◽  
Kai Hu
Keyword(s):  
Extracellular Matrix ◽  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Nucleus Pulposus Cells ◽  
Akt Inhibitor ◽  
Matrix Synthesis ◽  
Lncrna Gas5

The role of lncRNA growth arrest specific 5 (GAS5) in degenerative nucleus pulposus cell (NPC) apoptosis has been reported, but the mechanism of GAS5 in extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IDD) remains unknown. We aimed to investigate the mechanism of GAS5 in ECM synthesis in degenerative NPCs. GAS5 expression was measured in degenerative NPCs (CP-H170) and normal NPCs (CP-H097). siRNA-mediated GAS5 knockdown was transfected to NPCs to detect cell viability and the expression of ECM-related genes (Collagen II, aggrecan, Collagen I, and MMP-3). Subcellular localization of GAS5 was analyzed. The downstream gene and pathway of GAS5 in degenerative NPCs were explored. As our results indicated, lncRNA GAS5 was upregulated in degenerative NPCs. Silencing GAS5 improved the viability of degenerative NPCs and increased ECM synthesis. GAS5 was mainly located in the cytoplasm of NPCs. LncRNA GAS5 sponged miR-26a-5p to regulate PTEN. Overexpression of miR-26a-5p promoted ECM synthesis in degenerative NPCs. Akt inhibitor LY294002 reversed the promotion of silencing GAS5 on ECM synthesis of degenerative NPCs. In conclusion, lncRNA GAS5 sponged miR-26a-5p to upregulate PTEN and inhibit the PI3K/Akt pathway, thus inhibiting ECM synthesis of degenerative NPCs.

scholarly journals The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

2017 ◽  
Vol 97 (8) ◽  
pp. 971-982 ◽  
Author(s):  
Kun Wang ◽  
Wei Liu ◽  
Yu Song ◽  
Xinghuo Wu ◽  
Yukun Zhang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cells ◽  
Angiopoietin 2

scholarly journals FAM134B-Mediated ER-phagy Upregulation Attenuates AGEs-Induced Apoptosis and Senescence in Human Nucleus Pulposus Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Rongjin Luo ◽  
Shuai Li ◽  
Gaocai Li ◽  
Saideng Lu ◽  
Weifeng Zhang ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Vital Role ◽  
Nucleus Pulposus Cells ◽  
Ros Accumulation ◽  
Intracellular Ros ◽  
Glycation End Products ◽  
Ros Scavenger ◽  
Induced Apoptosis

Previous studies have established the pathogenic role of advanced glycation end products (AGEs) accumulation in intervertebral disc degeneration (IDD). Emerging evidence indicates that ER-phagy serves as a crucial cellular adaptive mechanism during stress conditions. This study is aimed at investigating the role of FAM134B-mediated ER-phagy in human nucleus pulposus (NP) cells upon AGEs treatment and exploring its regulatory mechanisms. We observed that AGEs treatment resulted in significantly increased apoptosis, senescence, and ROS accumulation in human NP cells; meanwhile, the enhanced apoptosis and senescence by AGEs treatment could be partially alleviated with the classic ROS scavenger NAC administration. Furthermore, we confirmed that FAM134B-mediated ER-phagy was activated under AGEs stimulation via ROS pathway. Importantly, it was also found that FAM134B overexpression could efficiently relieve intracellular ROS accumulation, apoptosis, and senescence upon AGEs treatment; conversely, FAM134B knockdown markedly resulted in opposite effects. In conclusion, our data demonstrate that FAM134B-mediated ER-phagy plays a vital role in AGEs-induced apoptosis and senescence through modulating cellular ROS accumulation, and targeting FAM134B-mediated ER-phagy could be a promising therapeutic strategy for IDD treatment.

Overexpression of miR-150 Inhibits the NF-κB Signal Pathway in Intervertebral Disc Degeneration through Targeting P2X7

2019 ◽  
Vol 207 (3-4) ◽  
pp. 165-176
Author(s):  
Yan Zhang ◽  
Yi-Shu Zhang ◽  
Xiao-Juan Li ◽  
Chao-Rong Huang ◽  
Hui-Jin Yu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Signal Pathway ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Collagen Ii ◽  
Cox 2

Objective: To elaborate the mechanism of miR-150 in the regulation of the NF-κB signal pathway in intervertebral disc degeneration (IDD) by targeting P2X7. Methods: The degenerative and normal intervertebral disc tissues were collected to detect the expressions of miR-150 and P2X7. Nucleus pulposus cells were transfected and divided into different groups. Cell apoptosis was determined by flow cytometry and TUNEL staining. The expressions of IL-6, TNF-α, MMP-3, MMP-13, Cox-2, iNOS, collagen II and aggrecan, as well as NF-κB-associated proteins were measured by qRT-PCR and Western blotting. Furthermore, IDD rat models were established to validate the role of miR-150 in vivo.Results: miR-150 was down-regulated but P2X7 was up-regulated in the degenerative intravertebral disc tissues. The apoptosis of nucleus pulposus cells in the IL-1β-induced group with the transfection of miR-150 mimic and siP2X7 was significantly decreased, with reduced levels of IL-6, TNF-α, MMP-3, MMP-13, Cox-2 and iNOS, increased levels of collagen II and aggrecan, as well as decreased P2X7, p-p65/p65 and cleaved caspase-3. However, the above factors showed an opposite tendency after treatment with miR-150 inhibitor. Furthermore, the P2X7 siRNA transfection could reverse the effects caused by miR-150 inhibitor. Simultaneously, pcDNA P2X7 transfection also inhibited the function of miR-150 mimic in IL-1β-induced nucleus pulposus cells. In vivoexperiments further verified the protective role of miR-150 in IDD rats. Conclusion: miR-150 may alleviate the degeneration of the intervertebral disc partially since it could restrict the NF-κB pathway by targeting P2X7, and thereby inhibiting IL-1β-induced matrix catabolism, inflammatory responses and apoptosis of the nucleus pulposus cells.

Role of Sirt1 Plays in Nucleus Pulposus Cells and Intervertebral Disc Degeneration

Spine ◽  
2017 ◽  
Vol 42 (13) ◽  
pp. E757-E766 ◽  
Author(s):  
Ji Guo ◽  
Minghao Shao ◽  
Feizhou Lu ◽  
Jianyuan Jiang ◽  
Xinlei Xia
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cells

scholarly journals Aloin Regulates Matrix Metabolism and Apoptosis in Human Nucleus Pulposus Cells via the TAK1/NF-κB/NLRP3 Signaling Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Taiqiu Chen ◽  
Pengfei Li ◽  
Jincheng Qiu ◽  
Wenjun Hu ◽  
Shaoguang Li ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Factors ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Matrix Metabolism ◽  
Colored Compound ◽  
Proinflammatory Factors ◽  
Promising Therapeutic Agent

Intervertebral disc degeneration (IDD) is a degenerative disease that is characterized by decreased matrix synthesis and extra degradation, nucleus pulposus cells (NPCs) apoptosis, and infiltration of inflammatory factors. Aloin, a colored compound from aloe plants, has been shown to be effective against skeletal degenerative diseases, but it is unclear whether it is protective against IDD. Herein, we investigated the role of aloin in NPCs. In our study, the upregulation of proinflammatory factors, apoptosis, and unbalanced matrix metabolism were observed in degenerative NP tissues. We found that aloin had a curative effect on extracellular matrix metabolism and apoptosis in TNF-alpha- (TNF-α-) treated NPCs by inhibiting oxidative stress and the proinflammatory factor expression. Further investigation revealed that aloin treatment suppressed the TAK1/NF-κB pathway. Moreover, the expression level of the NLPR3 inflammasome was downregulated after aloin treatment in TNF-α-treated NPCs. In summary, our results demonstrated that aloin treatment can reverse TNF-α-induced unbalanced matrix metabolism and apoptosis of NPCs via the TAK1/NF-κB/NLRP3 axis. This study supports that aloin can be a promising therapeutic agent for IDD.

Sign in / Sign up

Export Citation Format

Share Document