酸性 pH 通过激活 p38 MAPK 通路促进髓核细胞衰老。
Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MAPK pathway.
机构信息
Department of Orthopedics, Chongqing Medical University, Chongqing 400016, China.
Department of Orthopedics, Inner Mongolia Baogang Hospital, Baotou, Neimenggu 014010, China.
出版信息
Biosci Rep. 2018 Nov 13;38(6). doi: 10.1042/BSR20181451. Print 2018 Dec 21.
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 G/G 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.
背景
髓核（NP）细胞衰老（senescence）是退变椎间盘（degenerative disc）中的一个重要细胞特征。已知退变椎间盘内存在非常酸性的微环境（niche），其参与调节椎间盘细胞活力和基质代谢。
目的
本研究旨在探讨酸性 pH 在调节 NP 细胞衰老中的作用和潜在信号转导通路。
方法
将大鼠 NP 细胞在接近健康椎间盘的酸性 pH（7.2，对照组）或接近严重退变椎间盘的酸性 pH（6.2，实验组）下培养 10 天。此外，实验组的 NP 细胞与抑制剂 SB203580 共同孵育，以分析 p38 MAPK 通路在这一过程中的作用。
结果
与对照组 NP 细胞相比，实验组 NP 细胞增殖能力受到抑制，G/G 期细胞比例增加，S 期细胞比例减少，端粒酶活性降低，衰老相关分子（p16 和 p53）表达上调，基质相关分子（聚集蛋白聚糖和胶原 II）表达下调。进一步分析表明，p38 MAPK 通路的抑制部分逆转了酸性 pH 6.2 对实验组 NP 细胞的影响。
结论
在严重退变椎间盘内发现的非常酸性微环境通过调节 p38 MAPK 通路促进 NP 细胞衰老。本研究为椎间盘退变过程中 NP 细胞衰老提供了一种新的机制。
Zotero 插件