Intervertebral Disc Degeneration Research Articles

Identification of extracellular matrix proteins in plasma as a potential biomarker for intervertebral disc degeneration.

Recently, there has been significant focus on extracellular matrix proteolysis due to its importance in the pathological progression of intervertebral disc degeneration (IVDD). The present study investigates the circulating levels of extracellular matrix proteins in the plasma of IVDD and determines their potential relevance as biomarkers in disc degeneration. Global proteomic analysis was performed in the plasma samples of 10 healthy volunteers (HV) and 10 diseased subjects (DS) after depletion of highly abundant proteins such as albumin and IgG. We identified 144 and 135 matrix-associated proteins in plasma samples from healthy volunteers (HV) and patients with disc degeneration (DS), respectively. Among these, 49 of the matrix-associated proteins were identical to the proteins found in intervertebral disc (IVD) tissues retrieved from the in-house library. Applying stringent parameters, we selected 28 proteins, with 26 present in DS and 21 in HV. 19 proteins were found common between the groups, two of which-aggrecan (ACAN) and fibulin 1 (FBLN1) - showed statistically significant differences. Specifically, ACAN was up-regulated and FBLN1 was down-regulated in the DS-plasma. In particular, DS-plasma exhibited specific expression of collagen type 2a1 (COL2A1), native to the nucleus pulposus. The distinct presence of collagen type 2a1 and the elevated expression of aggrecan in IVDD plasma may serve as the basis for the development of a potential biomarker for monitoring the progression of disc degeneration.

The clinical significance of the Neutrophil-to-Lymphocyte Ratio as a novel inflammatory biomarker for assessing the severity of intervertebral disc degeneration

PurposeInflammation is integral to the pathogenesis of intervertebral disc degeneration, yet the role of systemic inflammatory markers in this process remains underexplored. This study aims to explore the association between the Neutrophil-to-Lymphocyte Ratio (NLR) and the severity of disc degeneration.Patients and methodsA retrospective analysis was conducted on 375 patients diagnosed with lumbar disc degeneration between April 2018 and May 2021. All patients underwent a complete blood cell count examination. We applied the Pfirrmann grading system for cumulative disc grading, stratifying patients into two groups: a high-score group (cumulative grade > 17) and a low-score group (cumulative grade ≤ 17), based on the median cumulative grade. The association between the NLR and and the severity of disc degeneration was further analyzed using correlation analysis and logistic regression models. Furthermore, the predictive capacity of the NLR for lumbar disc degeneration was assessed using the Receiver Operating Characteristic (ROC) curve.ResultsWe found a significant positive correlation between high NLR levels and severe disc degeneration. The high-score group exhibited a significantly higher NLR compared to the low-score group [2.63 (1.91–4.18) vs. 2.04 (1.38–2.74), respectively, p < 0.001]. Significant correlations were found between NLR and patient characteristics (including age, BMI, VAS, NSAIDs usage, hemoglobin) and the cumulative grading. Logistic regression analysis identified age and NLR as independent predictors of the severity of disc degeneration. The ROC curve analysis demonstrated a good predictive capability of NLR for lumbar disc degeneration.ConclusionNLR could serve as a promising biomarker for assessing the severity of lumbar disc degeneration and offer potential benefits in both early diagnosis and treatment strategies.

Combined Oxygen–Ozone and Porcine Injectable Collagen Therapies Boosting Efficacy in Low Back Pain and Disability

Background/Objectives: Intervertebral disc degeneration is the most common cause of low back pain (LBP), and lumbosciatica is a major challenge to healthcare systems worldwide. For years, ozone therapy has been used with excellent results in intervertebral disc disease and in patients with LBP. In vitro studies have demonstrated the positive action of porcine collagen in extracellular matrix remodeling and homeostasis. These tissue changes, associated with LBP, may suggest an indication for combined ozone/collagen treatment in patients with LBP. However, no studies have been reported regarding this combination of treatments. Methods: The present work compared retrospective data of two treatment groups (each of 10 LBP patients): (A) oxygen–ozone therapy (OOT) vs. (B) OOT plus porcine collagen type 1 injections (COL I). Pain intensity and physiological function were assessed by the numerical rating scale (NSR) method. The Roland–Morris questionnaire was used to assess disability. Patient data were acquired before, during, and at the six-month follow-up. Significant differences were assessed by ANOVA and Student’s t-test. Results: The analyses revealed significant statistical differences comparing the two arms, where the (OOT+COL I) treatment demonstrated a booster efficacy in pain (a reduction of 62% vs. 35%), while the questionnaire revealed a reduction in disability (70% vs. 31%). Conclusions: Therefore, this combination therapy (oxygen–ozone plus porcine injectable collagen) might be a promising approach for the management of patients with LBP.

From structure to therapy: the critical influence of cartilaginous endplates and microvascular network on intervertebral disc degeneration

The intervertebral disc (IVD) is the largest avascular structure in the human body. The cartilaginous endplate (CEP) is a layer of translucent cartilage located at the upper and lower edges of the vertebral bodies. On one hand, CEPs endure pressure from within the IVD and the tensile and shear forces of the annulus fibrosus, promoting uniform distribution of compressive loads on the vertebral bodies. On the other hand, microvascular diffusion channels within the CEP serve as the primary routes for nutrient supply to the IVD and the transport of metabolic waste. Degenerated CEP, characterized by increased stiffness, decreased permeability, and reduced water content, impairs substance transport and mechanical response within the IVD, ultimately leading to intervertebral disc degeneration (IDD). Insufficient nutrition of the IVD has long been considered the initiating factor of IDD, with CEP degeneration regarded as an early contributing factor. Additionally, CEP degeneration is frequently accompanied by Modic changes, which are common manifestations in the progression of IDD. Therefore, this paper comprehensively reviews the structure and physiological functions of CEP and its role in the cascade of IDD, exploring the intrinsic relationship between CEP degeneration and Modic changes from various perspectives. Furthermore, we summarize recent potential therapeutic approaches targeting CEP to delay IDD, offering new insights into the pathological mechanisms and regenerative repair strategies for IDD.

Regenerative Outcomes of Combining siCOL1A2 Hydrogel with Acupuncture in a Rat Model of Chronic Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is a significant cause of chronic pain and disability, necessitating innovative therapeutic strategies. This study investigates the combined effect of a novel siCOL1A2-encapsulated hydrogel and acupuncture on IVDD in a rat model. We developed a hydrogel system, siCOL1A2-encapsulated G5-PBA hydrogel (siCOL1A2@G5-PBA@Gel), designed for sustained siRNA delivery to the degenerated discs and assessed its therapeutic efficacy alongside acupuncture treatment. Key inflammatory genes were identified through RNA-seq analysis, with COL1A2 highlighted as a crucial regulator of inflammatory responses in IVDD. Our in vivo experiments involved treating rats with hydrogel alone, acupuncture alone, and combining both. The treatments were evaluated through behavioral pain assessments, imaging techniques (X-ray and MRI), and histological analyses. Results indicated that the combination therapy significantly alleviated pain, reduced inflammation, and promoted disc regeneration more effectively than individual treatments. The hydrogel proved biocompatible and facilitated targeted gene silencing, while acupuncture enhanced therapeutic outcomes by improving local blood circulation and modulating inflammatory responses. These findings suggest that integrating siCOL1A2 hydrogel with acupuncture offers a promising approach to treating IVDD.

Fiber‐Dependent 3D Anisotropic Stiffness‐Tunable Biomimetic Intervertebral Disc via Multi‐Material Additive Manufacturing

AbstractLumbar intervertebral disc degeneration is a global musculoskeletal disorder. Total disc replacement is an effective treatment for symptomatic degeneration unresponsive to conservative care. However, current artificial discs, with their joint‐like structural design and homogeneous materials, fail to replicate the 3D anisotropic stiffness of natural discs. Inspired by the intricate structure and material gradient of the natural disc, a biomimetic intervertebral disc is designed and fabricated using multi‐material additive manufacturing. The biomimetic disc exhibits 3D anisotropic stiffness similar to natural discs. By adjusting the hardness, diameter, and arrangement of fibers in annulus fibrosus, the biomimetic disc closely matches the 3D anisotropic stiffness of the natural lumbar disc, exceeding 90% similarity and outperforming existing artificial discs. This highlights the crucial role of fiber properties in disc stiffness regulation and enhances the understanding of biomechanical functions of structures and materials in the annulus fibrosus of human discs. These insights may inspire high‐performance artificial disc designs.

Development of a microfluidic system with a bearing micropump for applying fluid shear force in an intervertebral disc degeneration model involving mechanical stimulation

Background: The intervertebral disc (IVD) functions as a shock absorber with viscoelastic tissues, including the gelatinous nucleus pulposus and the collagenous annulus fibrosus (AF). External mechanical loading influences IVD homeostasis but can cause damage and inflammatory reactions, contributing to disc degeneration. There is a lack of in vitro platforms for modeling IVD disease with mechanical stimulation.Methods: This study aimed to create a mechanical stimulation-based model by subjecting AF cells to shear stress using a micropump system. A micropump platform was used to measure pulsation, flow rate, and shear stress. AF cells were exposed to fluid shear stress of 0.5 and 1 dyne/cm², and morphological changes, cytotoxicity, and cell viability were analyzed through a live/dead assay. Perimeter, area, diameter, and elongation were assessed using live cell imaging and imaging analysis software.Results: The micropump platform exhibited optimal rotor characteristics for uniform pulsation and shear stress. Fluid shear stress at 0.5 dyne/cm² showed no significant difference from the control group, while 1 dyne/cm² reduced cell adhesion and survival. Comparing the 0.5 dyne/cm² shear stress group and interleukin-1β group to the control, significant decreases in perimeter, area, and diameter were observed.Conclusion: The study successfully developed a micro-peristaltic pump platform for applying fluid shear stress to cells, identifying an optimal rotor for uniform stress application. The platform effectively modeled IVD disease, revealing reduced cell adhesion and survival under specific shear stress conditions. This platform has potential promise for discovering biomarkers and exploring cellular responsiveness to external stimuli.

Comparison of the long-term efficacy of ROI-C and conventional cage-plate in treatment of spinal cord injury without fracture or dislocation: a retrospective study

BackgroundThe self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in the treatment of cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been conducted on the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD.MethodsA total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. The cohort comprised 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients exhibited symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. The preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study.ResultsA total of 48 patients underwent ACDF with ROI-C, while 35 patients received a conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). However, statistical difference was found in disc height of fused segment and T1 slope between the two groups (P < 0.05). No statistical difference was in the incidence of cage subsidence (P > 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up.ConclusionOur study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.

Implementing enhanced recovery after surgery protocol in elderly patients following multi-level posterior lumbar or thoracolumbar instrumented fusion for degenerative diseases.

Enhanced recovery after surgery (ERAS) is an evidence-based multimodal perioperative management strategy. The aim of the present study was to analyze the clinical efficacy of ERAS in elderly patients (> 70 years old) undergoing multi-level posterior lumbar or thoracolumbar instrumented fusion for degenerative diseases. Patients older than 70 years undergoing multi-level lumbar or thoracolumbar instrumented fusion for degenerative disk diseases or spinal stenosis from January 2017 to December 2018 (non-ERAS group) and from January 2020 to December 2021 (ERAS group) were enrolled in present study. Patient-specific and procedure-specific clinical characteristics were collected. Univariate and multivariate regression were performed to determine the risk factors related to length of stay (LOS) and complications. A total of 233 patients were enrolled in this study, 70 in non-ERAS group and 163 in ERAS group. There were comparable baseline characteristics between groups. Further there were no significant differences in 90-day readmission rates and complication rates. However, we observed a significant reduction in LOS (14.89 ± 7.78 days in non-ERAS group versus 11.67 ± 7.26 days in ERAS group, p = 0.002) and overall number of complications (38 in non-ERAS group versus 58 in ERAS group, p = 0.008). Univariate linear regression denoted that operation time (p < 0.001), intraoperative blood loss (p < 0.001), intraoperative blood transfusion (p < 0.001), fusion number ≥ 5 (p < 0.001), spinal surgery including the thoracic spine (p < 0.001), CCI > 2 (p = 0.018), ERAS (p = 0.003) and spinal surgery including lumbar (p = 0.030) were associated with LOS. Furthermore, multivariate linear regression showed that ERAS (p = 0.001), CCI > 2 (p = 0.014), and Fusion number ≥ 5 (p = 0.002) were independent risk factors for LOS. Analogously, univariate logistic regression revealed that longer operation time (p = 0.005), more intraoperative blood loss (p < 0.001), more intraoperative blood transfusion (p = 0.001), fusion number ≥ 5 (p = 0.001), ERAS (p = 0.004) and spinal surgery including thoracic spine (p = 0.002) were related to complications, while implementing ERAS was associated with less complications. Multivariate logistic regression denoted that implementation of ERAS (p = 0.003), Intraoperative blood loss (p = 0.003) and Fusion number ≥ 5 (p = 0.008) were independent risk factors for postoperative complications. In conclusion, the present study reported the first ERAS principles performed in multi-level lumbar or thoracolumbar instrumented fusion for degenerative conditions. Our outcomes shown that the implementation of ERAS in these populations is favorable for reducing LOS and decreasing overall number of complications though the comparable complication rates between two groups. Totally, our ERAS protocols were safe and feasible in these populations.

A strong association between Modic changes type 2 and endplate defects at non-fused segments after ACDF

To determine the association between Modic changes (MC) with other MRI parameters and clinical symptoms of cervical degenerative disc disease (DDD). A retrospective analysis of data on patients with cervical DDD who underwent single-level anterior cervical discectomy and fusion. Preoperative demographic data (age, sex, surgical data) were collected, cervical MRI parameters (disc degeneration grade, MC and endplate defects, each determined at each cervical level) and clinical data (Numerical pain rating scale (NPRS) neck and arm, the Neck Disability Index (NDI)) were compared to preoperative data. The study included 121 patients at Visit 1 and 83 patients at Visit 2. The median follow-up duration was 26.5 [18.9; 33.1] months. Patients with MC had more intense NPRS-based neck pain before surgery compared to patients without MC (p=0.001). There were significant changes in MC rate at the C5-C6 levels due to a significant number of new MCs type 1 and MCs type 2 (p=0.002 and p<0.001, respectively). MC type 2 was associated with disc degeneration, endplate defects defects, patients' age and clinical scales (NDI, NPRS) (p<0.05). The endplate defects defect score threshold for predicting MC type 2 at the С3-С7 cervical levels was 5. The factor predicting MC type 2 at the C3-C7 cervical levels is submaximal damage to the endplate. The MC rate is increased due to MC type 1 and MC type 2. MC types at the cervical levels may not represent consecutive stages of the same process.

Vertebral Body Tethering for Thoracolumbar Curvatures in Adolescent Idiopathic Scoliosis: Radiographic and Clinical Outcomes at 2–6-Year Follow-Up

Background: The gold standard treatment for adolescent idiopathic scoliosis (AIS) is posterior spinal fusion (PSF). However, long-term consequences of PSF can include reduced spinal flexibility, back pain, and intervertebral disc degeneration. Vertebral body tethering (VBT) is a non-fusion alternative that preserves motion. We investigated the outcomes of VBT for the treatment of thoracolumbar (TL) major AIS in the largest single-surgeon series with a minimum 2-year follow-up (FU). Methods: We performed a retrospective single-center review. Inclusion criteria were AIS, Lenke 5/6 curvature, and skeletally immature Variables were compared using Student’s t-tests, Wilcoxon rank sum tests, Chi-square, and Fisher’s exact tests. Results: A total of 37 consecutive patients, age 14.1 ± 1.6 years, 86.5% F, 35.9 ± 11.5-month FU, were examined. Overall, 27 patients (73%) had Lenke 5 and 10 (27%) had Lenke 6 curvatures. Instrumentation of the TL curve alone was performed in 59.5%, and thoracic (T) and TL in 40.5% of patients. Overall, 45.9% of patients had two tethers placed in the TL spine; no patients had double tethers placed at the main thoracic curves. The TL (51 ± 8° to 20 ± 11°; p &lt; 0.0001) and T (37 ± 13° to 17 ± 10°; p &lt; 0.0001) curvatures improved from baseline to the latest FU. Overall, 89% of patients achieved major Cobb &lt; 35°; the three patients who did not experienced at least one cord breakage or required PSF. T5-T12 kyphosis increased (p = 0.0401) and lumbar lordosis was maintained (p = 0.9236). Both the TL inclinometer (16 ± 4º to 4 ± 2°; p &lt; 0.0001) and T (6 ± 4° to 4 ± 3°; p = 0.0036) measurements improved. There was a 49% tether breakage rate as follows: 60% for single-cord TL constructs and 35% for double cords (p = 0.0991). There was an 8.1% re-operation rate as follows: one conversion to T PSF and revision of the TL tether; one release of the T tether and revision of the TL tether; one screw revision for radiculopathy. One patient was re-admitted for poor pain control. Conclusions: Patients with TL major curvature treated with VBT experienced a high rate of clinically successful outcomes with maintenance of lumbar lordosis and relatively low complication rates at the latest FU.

Platelet Rich Plasma in the Management of Recurrent Lumbar Disc Surgery; A Study of Ten Cases

Low back pain (LBP) is a very common entity, now regarded as the first cause of disability worldwide. Intervertebral disc (IVD) degeneration leads to posterior rupture annulus fibrosus (AF) with extrusion of Central Nucleus pulposus (NP) through the injured area which has little potential to repair as it has no blood supply and causes mechanical pressure and inflammatory changes in the nerve root causing LBP. Autologous platelet rich plasma (PRP) contain concentrate blood that contain a natural concentration of autologous growth factors and cytokines and currently widely used in the clinical setting for tissue regeneration and repair. PRP had great potential to stimulate cell proliferation and metabolic activity of IVD effectively restoring structural change, improving matrix integrity, IVD regeneration, reducing discogenic back pain. Our Study of 10 cases, where repeat or re-exploration surgery (after primary PLID Surgery, fenestration and discectomy) was done, where removal of recurrent disc 5, release of epidural fibrosis and perineural scarring 4 and surgical debridement for discitis 1 was done. In addition, PRP was given in the disc space &amp; around the nerve root which provides lots of growth factor, cytokines which helps in disc regeneration and prevent adhesion &amp; fibrosis. These dual actions enhance symptomatic recovery of all cases. Large scale studies may be required to confirm the clinical evidence of PRP for the treatment of discogenic LBP Bang. J Neurosurgery 2024; 13(2): 70-74

Combined effect of artificial cervical disc replacement and facet tropism on the index-level facet joints: a finite element study

BackgroundArtificial Cervical Disc Replacement (ACDR) is an effective treatment for cervical degenerative disc diseases. However, clinical information regarding the facet joint alterations after ACDR was limited. Facet tropism is common in the sub-axial cervical spine. Our previous research indicated that facet tropism could lead to increased pressure on the cervical facet joints. This study aimed to assess the impact of facet tropism on the facet contact force and facet capsule stress after ACDR.MethodsA C2–T1 cervical finite element model was constructed from computed tomography (CT) scans of a 28-year-old male volunteer. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by altering the facet orientation at the C5-C6 level. The C5/C6 ACDR was simulated in the intact, moderate asymmetrical and severe asymmetrical models. A 75-N follower load with 1.0-Nm moments was applied to the top of C2 vertebra in the models to simulate flexion, extension, lateral bending, and axial rotation with the T1 vertebra fixed. The range of motions (ROMs) under all moments, facet contact forces (FCFs) and facet capsule strains were tested.ResultsIn the asymmetrical model, the right FCFs considerably increased under flexion, extension, right bending, left rotation, especially under right bending the right sided FCF of the severe asymmetrical model was about 5.44 times of the neutral position, and 3.14 times of the symmetrical model. and concentrated on the cephalad part of the facets. The facet capsule stresses on both sides remarkably increased under extension, lateral bending and right rotation. In the moderate and severe asymmetrical models, the capsule strain was greater on both sides of each position than in the symmetric model.ConclusionsThe face tropism increased facet contact force and facet capsule strain after ACDR, especially under extension, lateral bending, and rotation, and also could result in abnormal stress distribution on the facet joint surface and facet joint capsule. The results suggest that face tropism might be a risk factor for post-operative facet joint degeneration progression after ACDR. Facet tropism may be noteworthy when ACDR is considered as a surgical option.

PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription.

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses a considerable burden to society. However, the molecular mechanisms underlying IVDD remain to be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, and inflammatory responses in various diseases. Despite these regulatory functions, the mechanism of action of PRDM1 in IVDD remains unexplored. In this study, we investigated the role and underlying mechanisms of action of PRDM1 in IVDD progression. The expression of PRDM1 in nucleus pulposus (NP) tissues and NP cells (NPCs) was assessed using western blotting, immunohistochemistry, and immunofluorescence. The effects of PRDM1 on IVDD progression were investigated in vitro and in vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to confirm that PRDM1 triggered CASP1 transcription. Our study demonstrated for the first time that PRDM1 expression was substantially upregulated in degenerated NP tissues and NPCs. PRDM1 overexpression promoted NPCs pyroptosis by inhibiting mitophagy and exacerbating IVDD progression, whereas PRDM1 silencing exerted the opposite effect. Furthermore, PRDM1 activated CASP1 transcription, thereby promoting NPCs pyroptosis in vitro. Notably, CASP1 silencing reversed the effects of PRDM1 on the NPCs. To the best of our knowledge, this study is the first to demonstrate that PRDM1 silencing inhibits NPCs pyroptosis by repressing CASP1 transcription, which may be a promising new therapeutic target for IVDD.

New perspectives on YTHDF2 O-GlcNAc modification in the pathogenesis of intervertebral disc degeneration

This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.

Identifying critical modules and biomarkers of intervertebral disc degeneration by using weighted gene co-expression network.

Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein-protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells

Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1β) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.

Regional variations of mechanical responses of IVD to 7 different motions: An in vivo study combined with FEA and DFIS

The abnormal mechanical behaviour of a lumbar intervertebral disc (IVD) is commonly recognized as a direct indicator of intervertebral disc degeneration (IDD). However, current methods cannot evaluate the patient-specific mechanical performance of an IVD in vivo during movement. This study establishes a patient-specific (PS) model that combines the kinematics parameters of the lumbar spine obtained with a dual fluoroscopic imaging system (DFIS) and a finite-element (FE) method for the first time to reveal the mechanical behaviours of IVDs in vivo under seven motions. Three healthy participants were recruited for this study. CT images were obtained to create finite-element models of L3-L5 spine segments. Meanwhile, participants were required to take specific positions including upright standing, flexion, extension, left and right lateral bending, as well as left and right axial torsion in the DFIS. The in vivo kinematic parameters, calculated by registering the CT images with images obtained with DFIS, were considered as loading conditions in FE simulations. Significant differences of von Mises stresses and principal strains were found between PS model and GN model which employing a generalized moment as loading conditions, former resulting in up to 76.74 % lower strain than the GN model. Also, considerable differences were observed for five anatomical regions of the IVD (L3-L5). Under all motions, the stress in the centre region (nucleus pulposus) was the lowest, while the stress in the posterior region was the highest in extension motion. Therefore, activities such as stretching with an extension, should be avoided by patients with a herniated disc, in which the posterior region was the herniation site. The PS model combining in vivo kinematics and FE simulations shows the potential in the design and assessment of patient-specific implants.

Identification and Validation of Telomere-Related Gene Signature in Intervertebral Disc Degeneration

Identification and Validation of Telomere-Related Gene Signature in Intervertebral Disc Degeneration

Short Link N Modulates Inflammasome Activity in Intervertebral Discs Through Interaction with CD14.

Intervertebral disc degeneration and pain are associated with the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome activation and the processing of interleukin-1 beta (IL-1β). Activation of thehm inflammasome is triggered by Toll-like receptor stimulation and requires the cofactor receptor cluster of differentiation 14 (CD14). Short Link N (sLN), a peptide derived from link protein, has been shown to modulate inflammation and pain in discs in vitro and in vivo; however, the underlying mechanisms remain elusive. This study aims to assess whether sLN modulates IL-1β and inflammasome activity through interaction with CD14. Disc cells treated with lipopolysaccharides (LPS) with or without sLN were used to assess changes in Caspase-1, IL-1β, and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). Peptide docking of sLN to CD14 and immunoprecipitation were performed to determine their interaction. The results indicated that sLN inhibited LPS-induced NFκB and Caspase-1 activation, reducing IL-1β maturation and secretion in disc cells. A significant decrease in inflammasome markers was observed with sLN treatment. Immunoprecipitation studies revealed a direct interaction between sLN and the LPS-binding pocket of CD14. Our results suggest that sLN could be a potential therapeutic agent for discogenic pain by mitigating IL-1β and inflammasome activity within discs.