scholarly journals N‑cadherin attenuates nucleus pulposus cell senescence under high‑magnitude compression

2017 ◽  
Author(s):  
Ming Niu ◽  
Fei Ma ◽  
Jun Qian ◽  
Junwei Li ◽  
Tong Wang ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
High Magnitude

scholarly journals Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-κB pathway under high-magnitude compression

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Yanhai Jiang ◽  
Guozhang Dong ◽  
Yeliang Song
Keyword(s):  
Nucleus Pulposus ◽  
Bone Matrix ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
Ros Generation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
High Magnitude

Mechanical overloading is a risk factor of disc degeneration. Studies have demonstrated that resveratrol helps to maintain the disc cell’s healthy biology. The present study aims to investigate whether resveratrol can suppress mechanical overloading-induced nucleus pulposus (NP) cell senescence in vitro and the potential mechanism. The isolated rat NP cells were seeded in the decalcified bone matrix (DBM) and cultured under non-compression (control) and compression (20% deformation, 1.0 Hz, 6 h/day) for 5 days using the mechanically active bioreactor. The resveratrol (30 and 60 μM) was added into the culture medium of the compression group to investigate its protective effects against the NP cell senescence. NP cell senescence was evaluated by cell proliferation, cell cycle, senescence-associated β-galactosidase (SA-β-Gal) activity, telomerase (TE) activity, and gene expression of the senescence markers (p16 and p53). Additionally, the reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed. Compared with the non-compression group, the high-magnitude compression significantly promoted NP cell senescence, increased ROS generation and activity of the NF-κB pathway. However, resveratrol partly attenuated NP cell senescence, decreased ROS generation and activity of the NF-κB pathway in a concentration-dependent manner under mechanical compression. Resveratrol can alleviate mechanical overloading-induced NP cell senescence through regulating the ROS/NF-κB pathway. The present study provides that resveratrol may be a potential drug for retarding mechanical overloading-induced NP cell senescence.

scholarly journals The response of nucleus pulposus cell senescence to static and dynamic compressions in a disc organ culture

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Jianmin Shi ◽  
Lianglong Pang ◽  
Shouguo Jiao
Keyword(s):  
Organ Culture ◽  
Nucleus Pulposus ◽  
Dynamic Compression ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
Degenerative Changes ◽  
Mechanical Stimuli ◽  
Static Compression

Mechanical stimuli obviously affect disc nucleus pulposus (NP) biology. Previous studies have indicated that static compression exhibits detrimental effects on disc biology compared with dynamic compression. To study disc NP cell senescence under static compression and dynamic compression in a disc organ culture, porcine discs were cultured and subjected to compression (static compression: 0.4 MPa for 4 h once per day; dynamic compression: 0.4 MPa at a frequency of 1.0 Hz for 4 h once per day) for 7 days using a self-developed mechanically active bioreactor. The non-compressed discs were used as controls. Compared with the dynamic compression, static compression significantly promoted disc NP cell senescence, reflected by the increased senescence-associated β-galactosidase (SA-β-Gal) activity, senescence-associated heterochromatic foci (SAHF) formation and senescence markers expression, and the decreased telomerase (TE) activity and NP matrix biosynthesis. Static compression accelerates disc NP cell senescence compared with the dynamic compression in a disc organ culture. The present study provides that acceleration of NP cell senescence may be involved in previously reported static compression-mediated disc NP degenerative changes.

scholarly journals Upregulated lnc‑HRK‑2:1 prompts nucleus pulposus cell senescence in intervertebral disc degeneration

2020 ◽  
Vol 22 (6) ◽  
pp. 5251-5261
Author(s):  
Dongbo Liang ◽  
Dinggang Hong ◽  
Fuyu Tang ◽  
Yuan Wang ◽  
Jianfeng Li ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence

scholarly journals Role of p38–MAPK pathway in the effects of high-magnitude compression on nucleus pulposus cell senescence in a disc perfusion culture

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Lianglong Pang ◽  
Pei Li ◽  
Ruijie Zhang ◽  
Yuan Xu ◽  
Lei Song ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Ex Vivo ◽  
Mapk Pathway ◽  
Cell Senescence ◽  
Bioreactor Culture ◽  
Pathological Feature ◽  
High Magnitude ◽  
P38 Mapk Pathway

Nucleus pulposus (NP) cell senescence is a typical pathological feature within the degenerative intervertebral disc. As a potential inducing and aggregating factor of disc degeneration, mechanical overloading affects disc biology in multiple ways. The present study was to investigate the NP cell senescence-associated phenotype under intermittent high compression in an ex vivo disc bioreactor culture, and the role of the p38–MAPK pathway in this regulatory process. Porcine discs were cultured in culture chambers of a self-developed mechanically active bioreactor and subjected to different magnitudes of dynamic compression (low-magnitude and high-magnitude: 0.1 and 1.3 MPa at a frequency of 1.0 Hz for 2 h per day respectively) for 7 days. Non-compressed discs were used as controls. The inhibitor SB203580 was used to study the role of the p38–MAPK pathway in this process. Results showed that intermittent high-magnitude compression clearly induced senescence-associated changes in NP cells, such as increasing β-galactosidase-positive NP cells, decreasing PCNA-positive NP cells, promoting the formation of senescence-associated heterochromatic foci (SAHF), up-regulating the expression of senescence markers (p16 and p53), and attenuating matrix production. However, inhibition of the p38–MAPK pathway partly attenuated the effects of intermittent high-magnitude (1.3 MPa) compression on those described NP cell senescence-associated parameters. In conclusion, intermittent high-magnitude compression can induce NP cell senescence-associated changes in an ex vivo disc bioreactor culture, and the p38–MAPK pathway is involved in this process.

scholarly journals SIRT1 Attenuates Apoptosis of Nucleus Pulposus Cells by Targeting Interactions between LC3B and Fas under High-Magnitude Compression

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yunyun Zhuo ◽  
Haoming Wang ◽  
Luetao Zou ◽  
Yiyang Wang ◽  
Yanzhu Hu ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Nucleus Pulposus Cell ◽  
Nucleus Pulposus Cells ◽  
High Magnitude ◽  
Culture Model ◽  
Cellular Apoptosis ◽  
Rat Tail

Mechanical overloading-induced nucleus pulposus cell (NPC) apoptosis plays a core role in the pathogenesis of intervertebral disc degeneration. In this study, we investigated the involvement of mammalian silent information regulator 2 homolog (SIRT1) in NPC apoptosis under high-magnitude compression. Our results showed that high-magnitude compression aggravated cellular apoptosis and attenuated the expression levels of SIRT1 and microtubule-associated protein-1 light chain-3B (LC3B) in rat NPCs in a three-dimensional (3D) cell culture model and an in vivo rat tail compression model, whereas SIRT1 overexpression in NPCs partially reversed these indicators. Moreover, SIRT1 overexpression increased the formation of the LC3B/Fas complex, alleviated activation of the NF-κB pathway, and reduced NPC apoptosis. Finally, downregulation of LC3B partially activated the NF-κB pathway and aggravated NPC apoptosis. Overall, upregulation of SIRT1 increases formation of the LC3B/Fas complex, which contributes to suppression of NPC apoptosis by inhibiting the NF-κB pathway under high compressive stress.

In vitro and in vivo effects of hyperglycemia and diabetes mellitus on nucleus pulposus cell senescence

2022 ◽  
Author(s):  
Zengxin Jiang ◽  
Chang Jiang ◽  
Lixia Jin ◽  
Zixian Chen ◽  
Zhenzhou Feng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
In Vivo Effects

LncRNA H19 targets miR-22 to modulate H2 O2 -induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling

2018 ◽  
Vol 119 (6) ◽  
pp. 4990-5002 ◽  
Author(s):  
Xiaobin Wang ◽  
Mingxiang Zou ◽  
Jing Li ◽  
Bing Wang ◽  
Qianshi Zhang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence

scholarly journals N-Cadherin-Mediated Activation of PI3K/Akt-GSK-3β Signaling Attenuates Nucleus Pulposus Cell Apoptosis Under High-Magnitude Compression

2017 ◽  
Vol 44 (1) ◽  
pp. 229-239 ◽  
Author(s):  
Pei Li ◽  
Zherui Liang ◽  
Gang Hou ◽  
Lei Song ◽  
Ruijie Zhang ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Nucleus Pulposus Cell ◽  
Underlying Mechanism ◽  
Akt Pathway ◽  
Cell Phenotype ◽  
High Magnitude ◽  
Gsk 3Β

Background/Aims: Mechanical overloading-induced nucleus pulposus (NP) apoptosis plays an important role in the pathogenesis of intervertebral disc degeneration. N-cadherin (N-CDH)-mediated signaling preserves normal NP cell phenotype. This study aims to investigate the effects of N-CDH on NP cell apoptosis under high-magnitude compression and the underlying mechanism behind this process. Methods: Rat NP cells seeded on scaffold were perfusion-cultured using a self-developed perfusion bioreactor for 5 days and experienced different magnitudes (2% and 20% compressive deformation, respectively) of compression at a frequency of 1.0 Hz for 4 hours once per day. The un-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression and inhibitor LY294002 were used to further investigate the role of N-CDH and PI3K/Akt pathway under high-magnitude compression, respectively. NP cell apoptosis was evaluated by caspase-3 activity measured using a commercial kit, flow cytometry, and expression of apoptosis-related molecules analyzed by real-time PCR and western blotting assays. Results: High-magnitude compression significantly increased apoptotic NP cells, caspase-3 activity and expression of pro-apoptotic molecules (Bax and caspase-3/cleaved caspase-3), but decreased expression of anti-apoptotic molecule (Bcl-2). High-magnitude compression decreased expression of N-CDH, p-Akt and p-GSK-3β. However, N-CDH overexpression attenuated NP cell apoptosis and increased expression of p-Akt and p-GSK-3β under high-magnitude compression. Further analysis showed that inhibition of the PI3K/Akt pathway suppressed NP cell apoptosis and decreased expression of p-GSK-3β, but had no significant effects on N-CDH expression under high-magnitude compression. Conclusion: N-CDH can attenuate NP cell apoptosis through activating the PI3K/Akt-GSK-3β signaling under high-magnitude compression.

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