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Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

ABSTRACT: Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

SUBMITTER: Zhang XB

PROVIDER: S-EPMC8241771 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

Zhang Xiao-Bo XB Hu Yi-Cun YC Cheng Peng P Zhou Hai-Yu HY Chen Xiang-Yi XY Wu Ding D Zhang Rui-Hao RH Yu De-Chen DC Gao Xi-Dan XD Shi Jin-Tao JT Zhang Kai K Li Shao-Long SL Song Peng-Jie PJ Wang Ke-Ping KP

International journal of medical sciences 20210527 13

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly ind ...[more]

PMID: 34220308

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Project description:As a controllable biological process, regulated cell death (RCD) extensively participates in cellular homeostasis, organismal development, and the pathogenesis of diseases. This review addresses the research gaps by synthesising the findings on the complexity of RCD modes and their role in disc degeneration, and summarises the preclinical strategies to alleviate disc degeneration and promote disc repair by regulating RCD.BackgroundIntervertebral disc degeneration (IDD) is the major source of chronic low back pain. As a controllable biological process, regulated cell death (RCD) extensively participates in the pathogenesis of IDD. Nevertheless, the initiation and progression of RCD remain unclear, and more importantly, the interaction between different RCD modes during IDD and therapy is far from well understood.MethodsLiterature search was performed using "regulated cell death AND intervertebral disc degeneration" in PubMed, Embase, and Web of Science. Meanwhile, relevant findings have been reviewed and quoted.ResultsIn this review, we discuss the inducing factors of IDD, various modes of RCD in intervertebral disc, the interactions between different RCD modes, as well as the obstacles to achieve disc regeneration. Meanwhile, the research gaps and perspective in studies that targeting RCD are also presented.ConclusionIncreasing evidence demonstrated the presence of different RCD modes in intervertebral disc during the progression of IDD. RCD in the resident disc cells is probably induced by the multiple factors such as abnormal mechanical loading, nutritional imbalance, inflammation microenvironment, circadian rhythm changes, withdraw of hormones, and other biomechanical factors. A better understanding of the fundamental mechanisms and the interactions between different RCD modes might contribute to the rescuing of disc degeneration and development of promising therapeutics.Translational potential statementThe Translational potential of this article. This review aims to demonstrate a better understanding of the fundamental mechanisms governing RCD, which might contribute to the rescuing of disc degeneration and to the development of promising therapeutics in a clinical setting.

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Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

Publications

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

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