Abstract
Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell loss is closely related to IDD progression. Thus, investigating the specifically targeted therapeutic agents against NP cell loss depends on understanding the molecular mechanisms. In this study, human NP cells were treated with hydrogen peroxide (H2O2). Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) kit. The expression of circRNA arginine-glutamic acid dipeptide repeats (hsa_circ_RERE) and miR-299-5p was analyzed by real-time quantitative PCR. Western blot analysis was used to assess the protein expression levels. The autophagy levels in NP cells were detected by using an electronic microscope, LC3B protein immunofluorescence, and western blot. The apoptosis levels of NP cells were detected by flow cytometry and western blot. Dual-luciferase reporter assay analyzed the miR-299-5p bound to circ_RERE and galectin-3. Our results revealed that H2O2 significantly inhibited the viability of NP cells, promoted apoptosis and autophagy, and upregulated galectin-3 expression. miR-299-5p was reduced in IDD and H2O2-induced NP cells. The overexpression of miR-299-5p promoted cell viability and attenuated apoptosis and autophagy under H2O2 treatment. Besides, circ_RERE was upregulated in IDD and H2O2-induced NP cells. However, knockdown of circ_RERE reversed the effects of miR-299-5p overexpression on cell viability, apoptosis, and autophagy in NP cells. We propose that circ_RERE promotes the H2O2-induced apoptosis and autophagy of NP cells through the miR-299-5p/galectin-3 axis and may provide a new target for the clinical treatment of IDD.
Highlights
Disc degeneration is a pathological process that leads to the deterioration of intervertebral discs, the connective tissue between vertebrae which plays a crucial role in spinal kinematics.Several pathological changes in the intervertebral disc degeneration (IDD) are connected with disc degeneration, amongst which degradation of the extracellular matrix, inflammation, and cell loss are the most prevalent [1]
We found that galectin-3 is required for nucleus pulposus (NP) cell apoptosis and autophagy. hsa_circ_RERE sponges miR299-5p to induce galectin-3 expression in NP cell apoptosis and autophagy of IDD
Pathological evidence has shown that NP cell loss, which is closely related to the cell apoptosis and autophagy, increases the risk of IDD [33, 34]
Summary
Disc degeneration is a pathological process that leads to the deterioration of intervertebral discs, the connective tissue between vertebrae which plays a crucial role in spinal kinematics.Several pathological changes in the intervertebral disc degeneration (IDD) are connected with disc degeneration, amongst which degradation of the extracellular matrix, inflammation, and cell loss are the most prevalent [1].e intervertebral disc is composed of the outer annulus fibrosus and inner nucleus pulposus (NP) [2]. Disc degeneration is a pathological process that leads to the deterioration of intervertebral discs, the connective tissue between vertebrae which plays a crucial role in spinal kinematics.Several pathological changes in the intervertebral disc degeneration (IDD) are connected with disc degeneration, amongst which degradation of the extracellular matrix, inflammation, and cell loss are the most prevalent [1]. Inhibiting the loss of NP cells during IDD could be an effective strategy to prevent or reverse disc degeneration. Previous studies have shown that the expression of galectin-3 is upregulated in the NP cells and inhibition galectin-3 alleviates the spinal cord injury and IDD [7, 8]. Cell therapy may be an effective way to repair IDD; as a strong immune suppressor, TGF-β has been shown to inhibit inflammation respond effectively [9]. A previous study showed that the TGF-β suppresses galectin-3 expression through canonical Smad signaling and that galectin-3 synergizes catabolic actions of Journal of Healthcare Engineering
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