MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration

Zhang, Haijun; Liao, Hai-Yang; Bai, Deng-Yan; Wang, Zhiqiang; Xie, Xingwen

doi:10.1016/j.biopha.2021.112170

Cited by 74 publications

(58 citation statements)

References 98 publications

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“…Pathological activation of NF- κ B and MAPK signaling pathway has been closely associated with IVDD, including promoting ECM degradation, cell apoptosis, and inflammatory positive feedback loop [ 36 – 38 ]. In this present study, western blot demonstrated that CGRP could dose-dependently enhance the phosphorylation of MAPK (p38, ERK, and JNK) (Figures 6(a) and 6(b) ).…”

Section: Resultsmentioning

confidence: 99%

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

Sun

Zhu

Chang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Chronic low back pain (CLBP) has been proved to be the dominating cause of disability in patients with lumbar degenerative diseases. Of the various etiological factors, intervertebral disc degeneration (IVDD) has been the dominating cause. In the past few decades, the role and changes of nerve systems, especially the peripheral sensory fibers and their neurotransmitters, in the induction and progression of IVDD have attracted growing concerns. The expression of many neuropeptides, such as SP, NPY, and CGRP, in the nociceptive pathways is increased during the progression of IVDD and responsible for the discogenic pain. Here, the role of CGRP in the progression of IVDD was firstly investigated both in vitro and in vivo. Firstly, we confirmed that human degenerated intervertebral disc tissue exhibited elevated expression of CGRP and its receptor. Secondly, in vitro experiments suggested that CGRP could inhibit the proliferation and induce apoptosis in human nucleus pulposus (NP) cells, as well as promote inflammation and degenerated phenotypes through activating NF-κB and MAPK signaling pathways. Thirdly, CGRP receptor antagonist, Rimegepant, can ameliorate the adverse effects of CGRP imposed on NP cells, which were confirmed in vitro and in vivo. Our results will bring about a brand-new insight into the roles of neuromodulation in IVDD and related therapeutic attempts.

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Section: Resultsmentioning

confidence: 99%

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

Sun

Zhu

Chang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…MAPK1, also known as ERK, belongs to the MAPK family and is related to various cell processes, including proliferation, differentiation, transcription modulation, and development. MAPK is a mediator that regulates the downstream expression of proinflammatory cytokines and MMPs [35]. Numerous studies have demonstrated that MAPK1 is an important molecule that is associated with OA, and miRNA-186-5p downregulation inhibits OA development by targeting MAPK1 [36].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Zhang

Tian

et al. 2022

Membranes

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In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA.

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“…Autophagy is tightly connected to aging as well as apoptosis in the pathogenesis of disorders, including cancer, osteoarthritis, and degenerative diseases. Autophagy exists in degenerative disc and is an effective approach in regulating ECM metabolism in IVD ( Zhang et al, 2021b ). Related studies have elucidated that BMSC exosomes promote proliferation of AF cells by inhibiting expression of inflammatory cytokines stimulated by IL-1β.…”

Section: Potential Sources Of Applications By Exosomes During the Pro...mentioning

confidence: 99%

“…The mitogen-activated protein kinase (MAPK) family consists of ERK1/2, JNK, and p38 MAPK proteins, and studies show that ERK is mediated to cell proliferation and inflammation ( Sawe et al, 2008 ); p38 MAPKs are a type of proinflammatory mediator, and p38 MAPKs and JNK both modulate cell apoptosis and inflammation ( Yang et al, 2016 ; Lai et al, 2019 ). Increasing lines of evidence have shown that the activation of MAPK transduction is activated and tightly correlated to ECM degradation, cell aging, apoptosis, and inflammatory reactions in IDD ( Zhang et al, 2021b ). MLK3 belongs to serine/threonine MAPK kinase (MAP3K) and is aberrantly expressed in mammals, which mediates cell migration and invasion in various diseases ( Zhang et al, 2014a ; Lan et al, 2017 ; Misek et al, 2017 ).…”

Section: Potential Sources Of Applications By Exosomes During the Pro...mentioning

confidence: 99%

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Low back pain (LBP), which is one of the most severe medical and social problems globally, has affected nearly 80% of the population worldwide, and intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that happens to be the primary trigger of LBP. The pathology of IDD is based on the impaired homeostasis of catabolism and anabolism in the extracellular matrix (ECM), uncontrolled activation of immunologic cascades, dysfunction, and loss of nucleus pulposus (NP) cells in addition to dynamic cellular and biochemical alterations in the microenvironment of intervertebral disc (IVD). Currently, the main therapeutic approach regarding IDD is surgical intervention, but it could not considerably cure IDD. Exosomes, extracellular vesicles with a diameter of 30–150 nm, are secreted by various kinds of cell types like stem cells, tumor cells, immune cells, and endothelial cells; the lipid bilayer of the exosomes protects them from ribonuclease degradation and helps improve their biological efficiency in recipient cells. Increasing lines of evidence have reported the promising applications of exosomes in immunological diseases, and regarded exosomes as a potential therapeutic source for IDD. This review focuses on clarifying novel therapies based on exosomes derived from different cell sources and the essential roles of exosomes in regulating IDD, especially the immunologic strategy.

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MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration

Cited by 74 publications

References 98 publications

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

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