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Review
. 2024 Sep 19:12:1423665.
doi: 10.3389/fcell.2024.1423665. eCollection 2024.

The JNK signaling pathway in intervertebral disc degeneration

Ganggang Liu  1 , Lu Gao  1 , Yuncai Wang  1 , Xinsheng Xie  1 , Xuejiao Gao  2 , Xingjie Wu  1
Affiliations
Review

The JNK signaling pathway in intervertebral disc degeneration

Ganggang Liu et al. Front Cell Dev Biol. .

Abstract

Intervertebral disc degeneration (IDD) serves as the underlying pathology for various spinal degenerative conditions and is a primary contributor to low back pain (LBP). Recent studies have revealed a strong correlation between IDD and biological processes such as Programmed Cell Death (PCD), cellular senescence, inflammation, cell proliferation, extracellular matrix (ECM) degradation, and oxidative stress (OS). Of particular interest is the emerging evidence highlighting the significant involvement of the JNK signaling pathway in these fundamental biological processes of IDD. This paper explores the potential mechanisms through the JNK signaling pathway influences IDD in diverse ways. The objective of this article is to offer a fresh perspective and methodology for in-depth investigation into the pathogenesis of IDD by thoroughly examining the interplay between the JNK signaling pathway and IDD. Moreover, this paper summarizes the drugs and natural compounds that alleviate the progression of IDD by regulating the JNK signaling pathway. This paper aims to identify potential therapeutic targets and strategies for IDD treatment, providing valuable insights for clinical application.

Keywords: JNK path; cell proliferation, inflammation; cellular senescence (CS); extracellar matrix (ECM) degradation; intervertebral disc degeneration (IDD); oxidative stress (OS); programmed cell death (PCD).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) In normal IVD, the cell types in NP are notochord cells and NPCs, in AE are AF cells, and in CEP are chondrocytes. Neurovessels exist only in the outer layers of the AF and CEP. (B) The number of senescent and dead cells in the degenerated IVD continued to increase, cell density increased, and macrophages, T lymphocytes, and mast cells appeared. The density of microvessels in the endplate decreases, and nerve fibers and microvessels form compensatory growth into the inner layer of AF and even NP tissue. Loss of proteoglycans and water in the NP, reduced IVD height, AF rupture, and destruction or calcification of the CEP.
FIGURE 2
FIGURE 2
Schematic diagram of the JNK signaling pathway. When cells are stimulated by external stimuli or when receptors on the cell membrane bind to ligands, the JNK signaling pathway is triggered. The activation of this pathway is a three-stage cascade that begins with protein signaling. MAP3Ks (TAK1, MEKK1/4, ASK1, and MLK2/3) are activated in this pathway, further phosphorylating MKK4 or MKK7. JNK is also activated upon phosphorylation by MKK4 or MKK7. Then, activated JNK enters the nucleus, binds to transcription factors such as ATF2, Elk-1, and c-Jun, and regulates the specific gene expression by phosphorylating the active regions of these transcription factors. This process regulates physiological processes, such as cell growth, differentiation, and apoptosis.
FIGURE 3
FIGURE 3
The activation of JNK signaling pathway resulting in changes of various factors in IVD and eventually disc degeneration.
See this image and copyright information in PMC

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