High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway.
High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway.
复制标题
高强度压缩通过p38 MAPK-ROS途径加速髓核细胞的过早衰老
DOI：
10.1186/s13075-017-1384-z
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发表时间：
2017-09-18
影响因子：
4.9
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Li P;Hou G;Zhang R;Gan Y;Xu Y;Song L;Zhou Q
背景机械负荷过重可导致椎间盘退变。髓核（NP）细胞衰老在退变的椎间盘内加重。本研究旨在探讨高压缩对NP细胞衰老的影响和潜在的分子机制，这一进程MethodsRat NP细胞接种在脱钙骨matrix.MethodsRat NP细胞进行非压缩（控制）或压缩（2%或20%的变形，1.0 Hz，6小时/天）。利用活性氧（ROS）清除剂N-乙酰半胱氨酸（NAC）和p38 MAPK抑制剂SB 203580研究了ROS和p38 MAPK通路在高强度压力下的作用。此外，我们研究了压缩的影响，结果在支架和器官培养物中，高强度的压缩（0.1或1.3 MPa，1.0 Hz，6小时/天）均能使大鼠椎间盘组织产生明显的损伤。（20%变形或1.3 MPa）增加衰老相关β-半乳糖苷酶（SA-β-Gal）活性、衰老标志物（p16和p53）表达、G1细胞周期停滞和ROS产生，并降低细胞增殖、端粒酶活性和基质（聚集蛋白聚糖和胶原II）合成。20%变形组的进一步分析表明，NAC抑制NP细胞衰老，但对磷酸化p38 MAPK表达无明显影响，SB 203580显著减弱ROS生成和NP细胞senescence.ConclusionsHigh-magnitude压缩可通过p38 MAPK-ROS途径加速NP细胞衰老。
BackgroundMechanical overloading can lead to disc degeneration. Nucleus pulposus (NP) cell senescence is aggravated within the degenerated disc. This study was designed to investigate the effects of high compression on NP cell senescence and the underlying molecular mechanism of this process.MethodsRat NP cells seeded in decalcified bone matrix were subjected to non-compression (control) or compression (2% or 20% deformation, 1.0 Hz, 6 hours/day). The reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580 were used to investigate the roles of the ROS and p38 MAPK pathway under high-magnitude compression. Additionally, we studied the effects of compression (0.1 or 1.3 MPa, 1.0 Hz, 6 hours/day) in a rat disc organ culture.ResultsBoth in scaffold and organ cultures, high-magnitude compression (20% deformation or 1.3 MPa) increased senescence-associated β-galactosidase (SA-β-Gal) activity, senescence marker (p16 and p53) expression, G1 cell cycle arrest, and ROS generation, and decreased cell proliferation, telomerase activity and matrix (aggrecan and collagen II) synthesis. Further analysis of the 20% deformation group showed that NAC inhibited NP cell senescence but had no obvious effect on phospho-p38 MAPK expression and that SB203580 significantly attenuated ROS generation and NP cell senescence.ConclusionsHigh-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.
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影响因子：
2.7
作者：
Choi H;Johnson ZI;Risbud MV
通讯作者：
Risbud MV
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3
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Ariga, K;Yonenobu, K;Yoshikawa, H
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作者：
Gruber, Helen E.;Ingram, Jane A.;Hanley, Edward N., Jr.
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Hanley, Edward N., Jr.