Abstract
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-κB pathway, and reduced NPC apoptosis. Finally, downregulation of LC3B partially activated the NF-κB 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-κB pathway under high compressive stress.
Highlights
Intervertebral disc degeneration (IDD) is one of the main pathological causes of low back pain worldwide, which seriously reduces the quality of life of patients and brings a heavy socioeconomic burden [1]
SIRT1 expression was confirmed to be associated with cell apoptosis and autophagy in human NP tissues
Western blotting demonstrated the same results: SIRT1 and light chain-3B (LC3B) expression decreased, but cleaved caspase 3 expression increased in the IDD group (Figure 2(c))
Summary
Intervertebral disc degeneration (IDD) is one of the main pathological causes of low back pain worldwide, which seriously reduces the quality of life of patients and brings a heavy socioeconomic burden [1]. Intervertebral discs (IVDs) are heterogeneous structures with two facet joints that function as a “three-joint complex” to resist different mechanical loads and deformations in daily life movements, such as walking, bending, and leaning back [2]. It has been widely reported that high-magnitude compression can promote apoptosis and dyshomeostasis of the extracellular matrix (ECM) of NPCs and thereby accelerate the process of IDD [2, 5, 6]. Autophagy, characterized by autophagosome formation, is an evolutionarily conserved process through which the deleterious organelles and proteins induced by cellular stress can be eliminated [7, 8]. Previous studies have reported that autophagy interacts with apoptosis via an interaction between LC3B and FAS [15, 16].
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