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Regulated cell death: Implications for intervertebral disc degeneration and therapy
Fan Yang1, Weijian Liu1, Yongcan Huang2
1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
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.
Background:
Intervertebral 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.
Methods:
Literature 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.
Results:
In 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.
Conclusion:
Increasing 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 Statement:
The 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.
Insights
Regulated cell death (RCD) plays a key role in intervertebral disc degeneration (IDD). Understanding RCD mechanisms and interactions is crucial for developing new therapies to treat chronic low back pain caused by IDD.
Area of Science:
- Cell Biology
- Biomedical Science
- Regenerative Medicine
Background:
- Intervertebral disc degeneration (IDD) is a primary cause of chronic low back pain.
- Regulated cell death (RCD) is implicated in IDD pathogenesis, but its initiation, progression, and interplay between modes are poorly understood.
Purpose of the Study:
- To synthesize current research on RCD modes in IDD.
- To identify research gaps and preclinical strategies for alleviating IDD and promoting disc repair by targeting RCD.
Main Methods:
- Comprehensive literature search using keywords 'regulated cell death' and 'intervertebral disc degeneration' in major scientific databases (PubMed, Embase, Web of Science).
- Review and synthesis of relevant findings on RCD mechanisms and therapeutic strategies in IDD.
Main Results:
- Multiple RCD modes are present in intervertebral discs during IDD.
- Factors like mechanical stress, inflammation, and nutritional imbalance induce RCD in disc cells.
- Interactions between different RCD modes during IDD progression are complex and not fully elucidated.
Conclusions:
- Understanding the fundamental mechanisms and interactions of RCD modes in IDD is essential for developing effective therapeutic strategies.
- Targeting RCD holds promise for rescuing disc degeneration and advancing clinical treatments for chronic low back pain.
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