S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/ß-catenin signaling pathway: an in vitro and in vivo study.

BACKGROUND: Intervertebral disc degeneration (IDD) is a common musculoskeletal degenerative disease, which often leads to low back pain and even disability, resulting in loss of labor ability and decreased quality of life. Although many progresses have been made in the current research, the underlying mechanism of IDD remains unclear. The apoptosis of nucleus pulposus (NP) cells (NPCs) is an important pathological mechanism in intervertebral disc degeneration (IDD). This study evaluated the relationship between S100A6 and NPCs and its underlying mechanism. METHODS: Mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to screen and verify hub genes for IDD in human IVD specimens with different degeneration degrees. Western blotting, immunohistochemistry (IHC), and/or immunofluorescence (IF) were used to detect the expression level of S100A6 in human NP tissues and NPCs. The apoptotic phenotype of NPCs and Wnt/ß-catenin signaling pathway were evaluated using flow cytometry, western blotting, and IF. S100A6 was overexpressed or knocked down in NPCs to determine its impact on apoptosis and Wnt/ß-catenin signaling pathway activity. Moreover, we used the XAV-939 to inhibit and SKL2001 to activate the Wnt/ß-catenin signaling pathway. The therapeutic effect of S100A6 inhibition on IDD was also evaluated. RESULTS: S100A6 expression increased in IDD. In vitro, increased S100A6 expression promoted apoptosis in interleukin (IL)-1ß-induced NPCs. In contrast, the inhibition of S100A6 expression partially alleviated the progression of annulus fibrosus (AF) puncture-induced IDD in rats. Mechanistic studies revealed that S100A6 regulates NPC apoptosis via Wnt/ß-catenin signaling pathway. CONCLUSIONS: This study showed that S100A6 expression increased during IDD and promoted NPCs apoptosis by regulating the Wnt/ß-catenin signaling pathway, suggesting that S100A6 is a promising new therapeutic target for IDD.

Edaravone Improves Intermittent Hypoxia-Induced Cognitive Impairment and Hippocampal Damage in Rats.

Oxidative stress plays an essential role in obstructive sleep apnea-hypopnea syndrome-induced cognitive dysfunction in children. This study investigated the effects of edaravone, a potent free radical scavenger, on intermittent hypoxia (IH)-induced oxidative damage and cognition impairment in a young rat model of IH. IH rats were treated with edaravone for 4 weeks. Behavioral testing was performed using the Morris water maze, and hippocampal tissues were harvested for further analyses. Edaravone attenuated IH-induced cognitive impairment, reduced morphological and structural abnormalities, and increased the number of mitochondria in the IH rats. Furthermore, edaravone significantly increased the inhibition of hydroxyl free radicals; reduced expressions of superoxide anion, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine; and upregulated the expression of manganese superoxide dismutase, catalase, cAMP, protein kinase A, phosphorylated-cAMP response element-binding (p-CREB), B-cell lymphoma 2, and brain-derived neurotrophic factor in the hippocampal tissue of IH rats. Our findings suggest that edaravone attenuated IH-induced cognitive impairment and hippocampal damage by upregulating p-CREB in young rats.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.