Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy
Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy
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DOI：
10.1016/j.xnsj.2023.100210
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发表时间：
2023-06-01
影响因子：
--
通讯作者：
Kakutani, Kenichiro
中科院分区：
文献类型：
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作者：
Yurube, Takashi;Takeoka, Yoshiki;Kakutani, Kenichiro
背景资料：退行性椎间盘疾病是引起腰痛和相关神经症状的主要原因，是一个全球性的健康问题，具有高发病率，劳动力流失和社会经济负担。目前椎间盘切除和/或脊柱融合的手术策略导致载荷、减震和运动的功能丧失;因此，需要开发新的生物疗法。这一成就需要了解椎间盘细胞在衰老和退变过程中的命运。研究方法：通过文献综述，阐明了椎间盘细胞命运的当前概念和未来前景，重点是细胞凋亡、衰老和自噬。结果：椎间盘具有复杂的结构，包括髓核（NP）、纤维环（AF）和软骨终板。AF起源于间充质，NP起源于脊索。人类椎间盘NP脊索表型在青春期消失，伴随着细胞死亡诱导和软骨细胞增殖。椎间盘在形态学和生物化学上也从幼儿期开始退化，从而表明可能涉及细胞命运，包括疾病过程中与年龄相关的表型变化。由于椎间盘是人体最大的无血管器官，营养缺乏可能是导致椎间盘退变的原因。在衰老和退变过程中，椎间盘细胞经历衰老、不可逆的生长停滞、产生促炎细胞因子和基质降解酶。过度应激最终导致程序性细胞死亡，包括凋亡、坏死性凋亡、焦亡和铁亡。自噬是细胞内的降解和循环系统，在维持细胞内环境稳定中起着重要作用。虽然细胞凋亡和衰老的发生率随着年龄和退变的严重程度而增加，但自噬可以更早地被激活，以响应有限的营养和炎症，但在老化、退变的椎间盘中受损。磷脂酰肌醇3-激酶（PI 3 K）/Akt/哺乳动物雷帕霉素靶蛋白（mTOR）是决定椎间盘细胞命运的信号整合剂。结论：通过调节PI 3 K/Akt/mTOR信号传导调节细胞命运和微环境是退行性椎间盘疾病的潜在生物治疗。
Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. Methods: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. Results: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. Conclusions: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease.