Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics.
Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics.
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DOI：
10.22203/ecm.v036a13
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发表时间：
2018-10-18
影响因子：
3.1
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中科院分区：
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强健的细胞生物能量学在维持椎间盘基质稳态的能量需求过程中至关重要。椎间盘细胞生物能量学的下降被假设为有助于椎间盘退变中观察到的基质稳态扰动。本研究旨在测量衰老如何影响椎间盘细胞线粒体和生物能量学。测量的椎间盘相关变化包括椎间盘组织中的基质含量和细胞构成，以及从年轻（6-9个月）和老年（36-50个月）新西兰白色兔椎间盘分离的纤维环（AF）和髓核（NP）细胞培养物中的基质合成、细胞增殖和衰老标志物。使用Seahorse XFe 96分析仪测量细胞生物能量参数，以及定量线粒体形态学变化和膜电位。衰老减少线粒体数量和膜电位在这两种细胞类型。此外，它显着降低糖酵解能力，线粒体储备能力，最大有氧能力和非葡萄糖依赖性呼吸在NP。此外，NP细胞表现出与年龄相关的基质合成下降，并在较老的组织中细胞减少。尽管缺乏线粒体呼吸随年龄的变化，AF细胞显示糖酵解和改变基质生产的增加。虽然以前的研究报告了椎间盘细胞中与年龄相关的基质退行性变化，但本研究首次揭示了衰老影响线粒体数量和功能，特别是在NP细胞中。因此，与年龄相关的生物能量变化可能有助于老年NP细胞的功能改变，这是椎间盘退变的基础。
Robust cellular bioenergetics is vital in the energy-demanding process of maintaining matrix homeostasis in the intervertebral disc. Age-related decline in disc cellular bioenergetics is hypothesised to contribute to the matrix homeostatic perturbation observed in intervertebral disc degeneration. The present study aimed to measure how ageing impacted disc cell mitochondria and bioenergetics. Age-related changes measured included matrix content and cellularity in disc tissue, as well as matrix synthesis, cell proliferation and senescence markers in cell cultures derived from annulus fibrosus (AF) and nucleus pulposus (NP) isolated from the discs of young (6-9 months) and older (36-50 months) New Zealand White rabbits. Cellular bioenergetic parameters were measured using a Seahorse XFe96 Analyzer, in addition to quantitating mitochondrial morphological changes and membrane potential. Ageing reduced mitochondrial number and membrane potential in both cell types. Also, it significantly reduced glycolytic capacity, mitochondrial reserve capacity, maximum aerobic capacity and non-glucose-dependent respiration in NP. Moreover, NP cells exhibited age-related decline in matrix synthesis and reduced cellularity in older tissues. Despite a lack of changes in mitochondrial respiration with age, AF cells showed an increase in glycolysis and altered matrix production. While previous studies report age-related matrix degenerative changes in disc cells, the present study revealed, for the first time, that ageing affected mitochondrial number and function, particularly in NP cells. Consequently, age-related bioenergetic changes may contribute to the functional alterations in aged NP cells that underlie disc degeneration.