Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

Abstract

Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration.

N-Cadherin-Mediated Activation of PI3K/Akt-GSK-3β Signaling Attenuates Nucleus Pulposus Cell Apoptosis Under High-Magnitude Compression

“…The chronic and progressive matrix degradation is the main pathological character during disc degeneration [30, 31]. Cell apoptosis-induced decrease in NP cell number is the direct reason for the decrease in the NP matrix synthesis [6, 9, 32]. Therefore, deep investigation on the mechanism behind NP cell apoptosis will be helpful to understand pathogenesis of disc degeneration.…”

“…Cell death-caused cellular loss leads to decrease in matrix biosynthesis and plays an important role in promoting disc degeneration [6, 7]. As a common type of disc cell death, cell apoptosis is reported to be associated with disc degeneration [8, 9].…”

Roles of Non-Coding RNAs in Acute Kidney Injury

“…The intrinsic pathway is initiated intracellularly, and pro-apoptotic proteins are released from the mitochondria to activate caspases and trigger apoptosis [16]. The extrinsic pathway is mainly mediated through the Fas pathway [16]. The stimulation of cell surface death receptor Fas leads to receptor aggregation and the recruitment of the adaptor molecule FADD and procaspase-8, which subsequently becomes activated and initiates apoptosis by direct cleavage of downstream effector caspases [16].…”

“…Apoptosis is mediated by two main pathways: the mitochondrial pathway (intrinsic) and the cell death receptor-mediated pathway (extrinsic) [16]. The intrinsic pathway is initiated intracellularly, and pro-apoptotic proteins are released from the mitochondria to activate caspases and trigger apoptosis [16].…”

“…The extrinsic pathway is mainly mediated through the Fas pathway [16]. The stimulation of cell surface death receptor Fas leads to receptor aggregation and the recruitment of the adaptor molecule FADD and procaspase-8, which subsequently becomes activated and initiates apoptosis by direct cleavage of downstream effector caspases [16]. Puma, p53 upregulated modulator of apoptosis; PMAIP1, Phorbol-12-myristate-13-acetate-induced protein 1, also known as Noxa; Apaf-1, apoptotic protease activating factor-1; FADD, Fas-associated death domain; Bcl-2, B-cell lymphoma-2; Bid, BH3 interacting domain death agonist.…”