细胞生物学
炎症
化学
分解代谢
细胞外基质
合成代谢
西妥因1
信号转导
脂质代谢
重编程
MAPK/ERK通路
下调和上调
癌症研究
新陈代谢
生物
生物化学
细胞
免疫学
基因
作者
Yun Teng,Yixue Huang,Hao Yu,Cenhao Wu,Yan Qi,Yingjie Wang,Ming Yang,Haifeng Xie,Tianyi Wu,Huilin Yang,Jun Zou
标识
DOI:10.1016/j.apsb.2023.02.018
摘要
Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.
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