Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration

Abstract

Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain. IVDD is characterized by abnormal expression of extracellular matrix components such as collagen and aggrecan. In addition, it results in dysfunctional growth, senescence, and death of intervertebral cells. The biological pathways involved in the development and progression of IVDD are not fully understood. Therefore, a better understanding of the molecular mechanisms underlying IVDD could aid in the development of strategies for prevention and treatment. Autophagy is a cellular process that removes damaged proteins and dysfunctional organelles, and its dysfunction is linked to a variety of diseases, including IVDD and osteoarthritis. In this review, we describe recent research findings on the role of autophagy in IVDD pathogenesis and highlight autophagy-targeting molecules which can be exploited to treat IVDD. Many studies exhibit that autophagy protects against and postpones disc degeneration. Further research is needed to determine whether autophagy is required for cell integrity in intervertebral discs and to establish autophagy as a viable therapeutic target for IVDD.

siRNA incorporated in slow-release injectable hydrogel continuously silences DDIT4 and regulates nucleus pulposus cell pyroptosis through the ROS/TXNIP/NLRP3 axis to alleviate intervertebral disc degeneration

“…Immunofluorescence analysis revealed that the fluorescence intensity of DDIT4 was enhanced in NPCs treated with H 2 O 2 ( Figure 2c ). Western blotting showed that increased expression of DDIT4 in H 2 O 2 -treated NPC in a concentration-dependent manner was accompanied by a decrease in two important ECM-associated proteins, 33 COL2A1 and ACAN, and an increase in MMP13 and ADAMTS5, which are involved in the degradation of the ECM ( Figures 2d to 2i ). 34 To explore pyroptosis in NPCs under oxidative stress, the expression of NLRP3, ASC, cleaved GSDMD, cleaved CASP1, and IL-1β increased in a concentration-dependent manner in H 2 O 2 -treated NPCs (Supplementary Figure b).…”

Identification of Biomarkers, Pathways, Immune Properties of Mitophagy Genes, and Prediction Models for Intervertebral Disc Degeneration

“…Studies of degenerative rat NPCs have reported increased autophagy activity and up-regulation of autophagy-related genes compared with healthy disc tissue. 42 Recovery of autophagy flux can salvage oxidative damage and mitochondrial dysfunction to prevent disc degeneration. 43 Multiple studies have linked mitophagy to the initiation and development of disc degeneration.…”

The Survival of Human Intervertebral Disc Nucleus Pulposus Cells under Oxidative Stress Relies on the Autophagy Triggered by Delphinidin

“…Autophagy initiation has been suggested to protect against apoptosis in IVDD, underscoring its cytoprotective role [33,34]. While current research predominantly supports autophagy's preventive role in IVDD, some studies suggest its potential to accelerate the condition [35]. Autophagy reduces NP cell apoptosis, ECM degradation, senescence, and CEP inflammation and calcification, maintaining IVD ECM balance to prevent IVDD [36][37][38][39][40].…”