Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Orthopedics, Three Gorges Central Hospital, Chongqing 404000, China.
Oxid Med Cell Longev. 2021 Dec 27;2021:2420969. doi: 10.1155/2021/2420969. eCollection 2021.
Mechanical overloading-induced nucleus pulposus cell (NPC) apoptosis plays a core role in the pathogenesis of intervertebral disc degeneration. In this study, we investigated the involvement of mammalian silent information regulator 2 homolog (SIRT1) in NPC apoptosis under high-magnitude compression. Our results showed that high-magnitude compression aggravated cellular apoptosis and attenuated the expression levels of SIRT1 and microtubule-associated protein-1 light chain-3B (LC3B) in rat NPCs in a three-dimensional (3D) cell culture model and an in vivo rat tail compression model, whereas SIRT1 overexpression in NPCs partially reversed these indicators. Moreover, SIRT1 overexpression increased the formation of the LC3B/Fas complex, alleviated activation of the NF-B pathway, and reduced NPC apoptosis. Finally, downregulation of LC3B partially activated the NF-B pathway and aggravated NPC apoptosis. Overall, upregulation of SIRT1 increases formation of the LC3B/Fas complex, which contributes to suppression of NPC apoptosis by inhibiting the NF-B pathway under high compressive stress.
机械性超负荷诱导的髓核细胞（NPC）凋亡在椎间盘退变的发病机制中起核心作用。在这项研究中，我们研究了哺乳动物沉默信息调节因子 2 同源物（SIRT1）在高幅度压缩下 NPC 凋亡中的作用。我们的结果表明，在三维（3D）细胞培养模型和体内大鼠尾压缩模型中，高幅度压缩加剧了细胞凋亡，并减弱了大鼠 NPC 中 SIRT1 和微管相关蛋白 1 轻链 3B（LC3B）的表达水平，而 NPC 中的 SIRT1 过表达部分逆转了这些指标。此外，SIRT1 过表达增加了 LC3B/Fas 复合物的形成，减轻了 NF-B 途径的激活，并减少了 NPC 凋亡。最后，LC3B 的下调部分激活了 NF-B 途径并加重了 NPC 凋亡。总的来说，SIRT1 的上调增加了 LC3B/Fas 复合物的形成，通过抑制 NF-B 途径抑制 NPC 在高压缩应力下的凋亡。
