Role of autophagy in intervertebral disc degeneration.

Role of autophagy in intervertebral disc degeneration.
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DOI:
10.1002/jcp.30631
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发表时间:
2022-03
影响因子:
5.6
通讯作者:
Vo N
Vo N
中科院分区:
生物学2区
文献类型:
--
作者:
Kritschil R;Scott M;Sowa G;Vo N

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椎间盘退变(IDD)是导致腰痛的主要原因。椎间盘(IVD)由三种组织类型组成:中央凝胶状髓核(NP)组织、周围纤维环(AF)组织以及下软骨终板和上软骨终板。 IVD 微环境是低氧、酸性、高渗且营养物质含量低的,因为它大部分是无血管的。 IDD 起始和进展的细胞过程仍然知之甚少。具体来说,缺乏对 NP 细胞代谢和生理学的了解阻碍了治疗 IDD 患者的有效疗法的开发。自噬是一种重要的细胞内降解过程,可去除受损的细胞器、错误折叠的蛋白质和细胞内病原体,并回收降解的成分以提供细胞能量和功能。 NP 细胞利用很大程度上未知的过程适应了在恶劣的组织微环境中生存,我们假设自噬是这些未被发现的机制之一。在这篇综述中,我们描述了 IVD 组织的独特特征,回顾了生理应激源如何影响体外 NP 细胞的自噬,调查了目前对 IVD 中自噬调节的理解,并评估了自噬与 IDD 之间的关系。已发表的研究证实自噬标记物存在于 IVD 组织中,并且 IVD 细胞可以在体外调节自噬以响应细胞应激源。然而,仍然缺乏数据来确定 IVD 细胞中调节自噬的确切机制。需要更深入的研究来确定自噬是否是维持 IVD 细胞健康所必需的,并验证自噬作为治疗 IDD 的相关治疗靶点。
Intervertebral disc degeneration (IDD) is a leading contributor to low back pain. The intervertebral disc (IVD) is composed of three tissue types: the central gelatinous nucleus pulposus (NP) tissue, the surrounding annulus fibrosus (AF) tissue, and the inferior and superior cartilage endplates. The IVD microenvironment is hypoxic, acidic, hyperosmotic, and low in nutrients because it is mostly avascular. The cellular processes that underlie IDD initiation and progression are still poorly understood. Specifically, a lack of understanding regarding NP cell metabolism and physiology hinders the development of effective therapeutics to treat IDD patients. Autophagy is a vital intracellular degradation process that removes damaged organelles, misfolded proteins, and intracellular pathogens and recycles the degraded components for cellular energy and function. NP cells have adapted to survive within their harsh tissue microenvironment using processes that are largely unknown, and we postulate autophagy is one of these undiscovered mechanisms. In this review, we describe unique features of the IVD tissue, review how physiological stressors impact autophagy in NP cells in vitro, survey the current understanding of autophagy regulation in the IVD, and assess the relationship between autophagy and IDD. Published studies confirm autophagy markers are present in IVD tissue, and IVD cells can regulate autophagy in response to cellular stressors in vitro. However, data is still lacking to determine the exact mechanisms regulating autophagy in IVD cells. More in-depth research is needed to establish whether autophagy is necessary to maintain IVD cell health and validate autophagy as a relevant therapeutic target for treating IDD.
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