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 Osteogenic protein-1 attenuates apoptosis and enhances matrix synthesis of nucleus pulposus cells under high magnitude compression though inhibiting the p38 MAPK pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Haolin Fang ◽  
Xianzhou Li ◽  
Haiming Shen ◽  
Buwei Sun ◽  
Haijun Teng ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
High Magnitude ◽  
P38 Mapk Pathway ◽  
Regulated Expression ◽  
Osteogenic Protein

Disc degeneration is correlated with mechanical load. Osteogenic protein-1 (OP-1) is potential to regenerate degenerative disc. To investigate whether OP-1 can protect against high magitude compression-induced nucleus pulposus (NP) cell apoptosis and NP matrix catabolism, and its potential mechanism; porcine discs were cultured in a bioreactor and compressed at a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days. OP-1 was added along with the culture medium to investigate the protective effects of OP-1. NP cell apoptosis and matrix biosynthesis were evaluated. Additionally, activity of the p38 MAPK pathway is also analyzed. Compared with the control group, high magnitude compression significantly promoted NP cell apoptosis and decreased NP matrix biosynthesis, reflected by the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and caspase-3 activity, the up-regulated expression of Bax and caspase-3 mRNA and down-regulated expression of Bcl-2 mRNA, and the decreased Alcian Blue staining intensity and expression of matrix proteins (aggrecan and collagen II). However, OP-1 addition partly attenuated the effects of high magnitude compression on NP cell apoptosis and NP matrix biosynthesis. Further analysis showed that inhibition of the p38 MAPK pathway partly participated in this process. OP-1 can attenuate high magnitude compression-induced NP cell apoptosis and promoted NP matrix biosynthesis, and inhibition of the p38 MAPK pathway may participate in this regulatory process. The present study provides that OP-1 may be efficient in retarding mechanical overloading-exacerbated disc degeneration.

scholarly journals Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MAPK pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jiabin Fu ◽  
Wei Yu ◽  
Dianming Jiang
Keyword(s):  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Cell Senescence ◽  
Phase Fraction ◽  
Control Group ◽  
Acidic Ph ◽  
Degenerative Disc ◽  
P38 Mapk Pathway ◽  
Regulated Expression

Background: Nucleus pulposus (NP) cell senescence is an important cellular feature within the degenerative disc. It is known that a very acidic niche exists in the degenerative disc, which participates in regulating disc cell viability and matrix metabolism. Objective: The present study was aimed to investigate the role and potential signaling transduction pathway of an acidic pH in regulating NP cell senescence. Methods: Rat NP cells were cultured in an acidic pH of 7.2 close to that in a healthy disc (Control group) or in an acidic pH of 6.2 close to that in a severe degenerative disc (Experiment group) for 10 days. Additionally, the experimental NP cells were incubated along with the inhibitor SB203580 to analyze the role of p38 MAPK pathway in this process. Results: Compared with the control NP cells, experimental NP cells showed a suppressed cell proliferation potency, an increased G0/G1 phase fraction whereas a decreased S-phase fraction and a declined telomerase activity, an up-regulated expression of senescence-related molecules (p16 and p53), and a down-regulated expression of matrix-related moleucles (aggrecan and collagen II). Further analysis showed that inhibition of the p38 MAPK pathway partly reversed effects of acidic pH of 6.2 on the experimental NP cells. Conclusion: The very acidic niche identified in a severe degenerative disc promotes NP cell senescence through regulating the p38 MAPK pathway. The present study provides a new mechanism that drives NP cell senescence during disc degeneration.

Role of the p38 MAPK Pathway in Induction of iNOS Expression in Human Leukocytes

2008 ◽  
Vol 56 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Ewa Jablonska ◽  
Wioletta Ratajczak ◽  
Jakub Jablonski
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Inos Expression ◽  
Human Leukocytes ◽  
P38 Mapk Pathway

Anti-inflammatory role of Leptin in glial cells through p38 MAPK pathway inhibition

2017 ◽  
Vol 69 (3) ◽  
pp. 409-418 ◽  
Author(s):  
Iván Patraca ◽  
Nohora Martínez ◽  
Oriol Busquets ◽  
Aleix Martí ◽  
Ignacio Pedrós ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Glial Cells ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Anti Inflammatory ◽  
Pathway Inhibition

scholarly journals Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

2016 ◽  
Vol 39 (6) ◽  
pp. 2216-2226 ◽  
Author(s):  
Pei Li ◽  
Yuan Xu ◽  
Yibo Gan ◽  
Liyuan Wang ◽  
Bin Ouyang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Matrix Synthesis ◽  
P38 Mapk Pathway ◽  
Collagen Ii

Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP) tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E2) in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10-5, 10-7 and 10-9 M) or without (control) E2 for48 hours. The estrogen receptor (ER)-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG) content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway

2018 ◽  
Vol 372 (2) ◽  
pp. 158-167 ◽  
Author(s):  
Huimin Chen ◽  
Shuyu Guo ◽  
Yang Xia ◽  
Lichan Yuan ◽  
Mengting Lu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Root Development ◽  
Mapk Pathway ◽  
Tooth Root ◽  
P38 Mapk Pathway ◽  
Rho Gef

scholarly journals Mechano growth factor attenuates mechanical overload-induced nucleus pulposus cell apoptosis through inhibiting the p38 MAPK pathway

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Qing Xu ◽  
Haolin Fang ◽  
Liang Zhao ◽  
Cunxin Zhang ◽  
Luo Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Mechanical Overload

Abstract Mechanical overload is a risk factor of disc degeneration. It can induce disc degeneration through mediating cell apoptosis. Mechano growth factor (MGF) has been reported to inhibit mechanical overload-induced apoptosis of chondrocytes. The present study is aimed to investigate whether MGF can attenuate mechanical overload-induced nucleus pulposus (NP) cell apoptosis and the possible signaling transduction pathway. Rat NP cells were cultured and subjected to mechanical overload for 7 days. The control NP cells did not experience mechanical load. The exogenous MGF peptide was added into the culture medium to investigate its protective effects. NP cell apoptosis ratio, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3, protein expression of cleaved caspase-3, cleaved PARP, Bax and Bcl-2 were analyzed to evaluate NP cell apoptosis. In addition, activity of the p38 MAPK pathway was also detected. Compared with the control NP cells, mechanical overload significantly increased NP cell apoptosis and caspase-3 activity, up-regulated gene/protein expression of pro-apoptosis molecules (i.e. Bax, caspase-3, cleaved caspase-3 and cleaved PARP) whereas down-regulated gene/protein expression of anti-apoptosis molecule (i.e. Bcl-2). However, exogenous MGF partly reversed these effects of mechanical overload on NP cell apoptosis. Further results showed that activity of the p38 MAPK pathway of NP cells cultured under mechanical overload was decreased by addition of MGF peptide. In conclusion, MGF is able to attenuate mechanical overload-induced NP cell apoptosis, and the p38 MAPK signaling pathway may be involved in this process. The present study provides that MGF supplementation may be a promising strategy to retard mechanical overload-induced disc degeneration.

The role of p38 MAPK pathway in p53 compromised state and telomere mediated DNA damage response

2018 ◽  
Vol 836 ◽  
pp. 89-97 ◽  
Author(s):  
Shomereeta Roy ◽  
Souvick Roy ◽  
Aarti Rana ◽  
Yusuf Akhter ◽  
Manoor Prakash Hande ◽  
...  
Keyword(s):  
Dna Damage ◽  
P38 Mapk ◽  
Dna Damage Response ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Damage Response

scholarly journals The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis

Oncogene ◽  
2006 ◽  
Vol 26 (17) ◽  
pp. 2502-2506 ◽  
Author(s):  
O N Demidov ◽  
C Kek ◽  
S Shreeram ◽  
O Timofeev ◽  
A J Fornace ◽  
...  
Keyword(s):  
Mammary Gland ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
P38 Mapk Pathway
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