Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells

作者：Daqian Zhou, Yongliang Mei, Chao Song, Kang Cheng, Weiye Cai, Daru Guo, Silong Gao, Jiale Lv, Tao Liu, Yang Zhou, Liquan Wang, Bing Liu, Zongchao Liu · 发表于：European Journal of Clinical Investigation · 年份：2024 · DOI：10.1111/eci.14226 · 被引用次数：36 · 研究领域：Spine and Intervertebral Disc Pathology、Inflammasome and immune disorders、Spondyloarthritis Studies and Treatments

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes a heavy economic burden on people and society. Although it is well established that IVDD is associated with genetic susceptibility, ageing and obesity, its pathogenesis remains incompletely understood. Previously, IVDD was thought to occur because of excessive mechanical loading leading to destruction of nucleus pulposus cells (NPCs), but studies have shown that IVDD is a much more complex process associated with inflammation, metabolic factors and NPCs death and can involve all parts of the disc, characterized by causing NPCs death and extracellular matrix (ECM) degradation. The damage pattern of NPCs in IVDD is like that of some programmed cell death, suggesting that IVDD is associated with programmed cell death. Although apoptosis and pyroptosis of NPCs have been studied in IVDD, the pathogenesis of intervertebral disc degeneration can still not be fully elucidated by using only traditional cell death modalities. With increasing research, some new modes of cell death, PANoptosis, ferroptosis and senescence have been found to be closely related to intervertebral disc degeneration. Among these, PANoptosis combines essential elements of pyroptosis, apoptosis and necroptosis to form a highly coordinated and dynamically balanced programmed inflammatory cell death process. Furthermore, we believe that PANoptosis may also crosstalk with pyroptosis and senescence. Therefore...