Risk Of Intervertebral Disc Degeneration Research Articles

Diabetes Mellitus and Intervertebral Disc Degeneration: A Meta-Analysis

BackgroundDiabetes mellitus (DM) has been related to a higher risk of intervertebral disc degeneration (IVDD). However, the previous studies showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively investigate the association between DM and IVDD in adult population. MethodsObservational studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. ResultsEleven observational studies involving 2881170 adults were included. Among them, 1211880 had DM. Compared to those with normoglycemia, patients with DM were associated with a higher odds ratio (OR) of IVDD (OR: 1.68, 95% confidence interval [CI]: 1.24 to 2.29, p < 0.001; I2= 98%). Further sensitivity analysis excluding database studies with IVDD diagnosed via International Classification of Disease codes showed consistent results (OR: 1.47, 95% CI: 1.06 to 2.02, p = 0.02) with no statistical heterogeneity (I2 = 0%). Subgroup analyses showed a stronger association between DM and IVDD in cohort studies than that in cross-sectional studies, in studies evaluating overall IVDD than that evaluating lumbar disc degeneration, and in studies that adjusted age and body mass index (BMI) than that did not (p for subgroup differences all < 0.05). Subgroup analyses according to study country and quality score did not significantly affect the association. ConclusionsDM may be associated with IVDD in adult population, which seems to be independent of age and BMI.

Causal relationship between intervertebral disc degeneration and osteoporosis: a bidirectional two-sample Mendelian randomization study.

The relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated. The genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. No significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123-1.284, P = 8.72 × 10-8; LS-BMD: IVW, OR = 1.179, 95% CI: 1.083-1.284, P = 1.43 × 10-4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008-1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041-1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05). OP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.

Evaluating the causal effect of atherosclerosis on the risk of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) and atherosclerosis are two common age-related conditions that can cause significant morbidity. While previous studies have suggested an association between the two conditions, the nature of this association remains unclear. We used Mendelian randomization (MR) to investigate the causal relationship between IDD and atherosclerosis. We identified genetic variants associated with IDD using summary statistics from a large genome-wide association study (GWAS). These variants were then used as instrumental variables to infer causal relationships with atherosclerosis in summary statistics from a separate GWAS. Our MR analysis provided evidence for a causal relationship between IDD and atherosclerosis. We found that the genetic predisposition to atherosclerosis was associated with a higher risk of IDD (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.07-11.74, p = 0.04). The IVW estimates were consistent with the observational findings and other robust MR methods. Sensitivity analyses suggested that our findings were robust to potential sources of bias. Our study provides evidence for a causal link between IDD and atherosclerosis, suggesting that interventions targeting atherosclerosis could have potential benefits for reducing the risk of IDD. Further research is needed to explore the underlying mechanisms that link these two conditions and to investigate potential therapeutic interventions.

Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization.

Intervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated. We obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR. In total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD. Our findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.

Unravelling diagnostic clusters and immune landscapes of cuproptosis patterns in intervertebral disc degeneration through dry and wet experiments.

Cuproptosis is a manner of mitochondrial cell death induced by copper. However, cuproptosis modulators' molecular processes in intervertebral disc degeneration (IDD) are still unclear. To better understand the processes of cuproptosis regulators in IDD, a thorough analysis of cuproptosis regulators in the diagnostic biomarkers and subtype determination of IDD was conducted. Then we collected clinical IDD samples and successfully established IDD model in vivo and in vitro, and carried out real-time quantitative polymerase chain reaction (RT-qPCR) validation of significant cuproptosis modulators. Totally we identified 8 crucial cuproptosis regulators in the present research. Using a random forest model, we isolated 8 diagnostic cuproptosis modulators for the prediction of IDD risk. Then, based on our following decision curve analysis, we selected the five diagnostic cuproptosis regulators with importance scores greater than two and built a nomogram model. Using a consensus clustering method, we divided IDD patients into two cuproptosis clusters (clusterA and clusterB) based on the important cuproptosis regulators. Additionally, each sample's cuproptosis value was evaluated using principal component analysis in order to quantify the cuproptosis clusters. Patients in clusterB had higher cuproptosis scores than patients in clusterA. Moreover, we found that clusterB was involved in the immunity of natural killer cell, while clusterA was related to activated CD4 T cell, activated B cell, etc. Notably, cuproptosis modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. To sum up, cuproptosis modulators play a crucial role in the pathogenic process of IDD, providing biomarkers and immunotherapeutic approaches for IDD.

Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study

To investigate the causal relationship between sarcopenia (SP) and intervertebral disc degeneration (IVDD) using two-sample Mendelian randomization analysis. Genome-wide association study (GWAS) databases of SP (lean body mass, right and left hand grip strength) and IVDD were obtained. The single nucleotide polymorphisms (SNPs) strongly associated with exposure were obtained as an instrumental variable. After conservatively removing two confounders (smoking and sedentary life style), the causal relationship between SP and IVDD was assessed using Mendelian randomization analyses through the inverse variance weighting (IVW), weighted median (WM) and MR-Egger methods. The consistency and accuracy of the results were verified by MR-PRESSO, double validation, negative control, heterogeneity and diversity tests. A total of 570 SNPs associated with lean muscle mass, 97 with strong right hand grip strength, and 79 with strong left hand grip strength were included in the analysis. The results showed that lean muscle mass had a significant positive correlation with IVDD (IVW: OR=1.139, 95% CI: 1.076-1.204, P=6.619e-6) and right hand grip strength had a possible positive correlation with IVDD. After reanalysis in MR-PRESSO and selection of a new IVDD database, the results remained largely consistent with the previous results. Increased muscle mass may increase the risk of intervertebral disc degeneration.

Pan-cancer analysis of the intervertebral-disc-degeneration-related innate immunity gene NAIP.

Intervertebral disc degeneration (IDD) is a progressive chronic condition that commonly causes low back pain. Cancer is among the primary reasons for deaths worldwide. Our purpose was to identify the characteristic genes of IDD and explore the potential association between IDD and cancer. Immune cell infiltration and differentially expressed analysis were conducted utilizing data from the GSE124272 database. Enrichment analysis of differentially expressed genes (DEGs) was performed to explore the possible mechanisms underlying IDD development. Moreover, weighted gene correlation network analysis (WGCNA) was applied to select IDD-related hub genes. The immune-related key genes were determined by intersecting DEGs, IDD-related hub genes, and immune genes. Subsequently, machine learning models based on these genes were built to identify and verify the characteristic genes. RNA sequencing and clinical data of 33 carcinoma categories were obtained from the Cancer Genome Atlas (TCGA). The association between NAIP expression and prognosis was calculated using the Kaplan-Meier analysis. To gain a deeper understanding of the impact of NAIP in tumor immunotherapy, the association between NAIP and immune infiltration and two immunotherapeutic biomarkers were explored. Ultimately, the association between NAIP and immunotherapeutic response was investigated utilizing two independent cohorts. NAIP was identified as an immune-related characteristic gene between IDD and normal intervertebral disc tissue. In certain carcinoma categories, NAIP expression levels were elevated (4/33) and significantly correlated to the respective tumor stage (4/21). Survival analysis revealed that the expression levels of NAIP have prognostic significance in different cancer types. Generally, NAIP presented a strong association with immune cell infiltration and modulators. NAIP may influence immunotherapy effects through tumor mutational burden and microsatellite instability. No remarkable association between NAIP and immunotherapy response was found in either cohort. Our study is the first to identify NAIP as an immune-related characteristic gene. Pan-cancer analysis revealed that NAIP could serve as a novel clinical prognostic marker and therapeutic target for a variety of carcinoma categories, reducing the risk of IDD in tumor patients.

Sequencing and bioinformatics analysis of miRNA from rat endplate chondrogenic exosomes.

Exosomes have a key role in various diseases, such as arthritis, heart disease and respiratory disease. Exosomes from various sources have also been indicated to improve intervertebral disc degeneration. However, the role of endplate chondrogenic exosomes in intervertebral disc degeneration has remained largely elusive. The aim of the present study was to compare exosomal microRNA (miRNA) expression patterns in endplate chondrocytes before and after degeneration, and their potential roles in the pathogenesis of intervertebral disc degeneration (IVDD). Endplate chondrocytes were extracted from rats and cultured to obtain pre- and post-degeneration chondrocytes. Exosomes were obtained from the chondrocytes by centrifugation. The two groups of exosomes were subjected to small RNA sequencing, miRNA identification, novel miRNA prediction, quantitative analysis of miRNA expression and differentially expressed (DE) miRNA screening, in addition to miRNA target gene (TG) prediction and TG functional annotation and enrichment analysis. The percentage of miRNAs isolated from the exosomes before and after degeneration was found to differ. A total of 58 DE miRNAs were analyzed, the expression levels of which were significantly different post-degeneration compared with pre-degeneration. Cell experiments were also performed, in which the exosomes were co-cultured with nucleus pulposus (NP) cells. The results indicated that the chondrocyte-derived exosomes were taken up by the NP cells and influenced the expression of aggrecan and collagen 1A and 2A, suggesting that they may inhibit IVDD via their action on NP cells. The specific miRNAs present in exosomes during IVDD may be used to develop new targets for the treatment and diagnosis of this condition. DE exosomal miRNAs derived from endplate cartilage pre- and post-degeneration may be associated with the risk of IVDD and could help to distinguish patients with IVDD. Furthermore, the expression of certain miRNAs may be associated with disease progression, which may contribute to understanding the pathophysiology of IVDD from an epigenetic perspective.

Impact of dyslipidemia on the severity of symptomatic lumbar spine degeneration: A retrospective clinical study.

Lumbar intervertebral disc degeneration (IVDD) is an important cause of low back pain or sciatica, and metabolic factors play an important role. However, little is known about the relationship of dyslipidemia to the risk of intervertebral disc degeneration (IVDD). This study aimed to assess the impact of serum lipid levels on the severity of lumbar disc degeneration and to investigate its association with endplate inflammation. We conducted a case retrospective study in which a total of 302 hospitalized Chinese patients were recruited, of whom 188 (112 males and 76 females; mean age: 51.66 years) were without underlying disease, while the remaining 114 patients (51 males and 63 females; mean age: 62.75 years) had underlying diseases. We examined fasting serum lipid levels for total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Magnetic resonance imaging (MRI) was used to determine endplate inflammation. Pfirrmann grading and Weishaupt grading were used to evaluate the severity of intervertebral disc degeneration and facet joint degeneration, respectively. There was no difference in age, gender, and general BMI between the two groups (P > 0.05), but there were significantly high levels in TC, LDL-C, and LDL-C/HDL-C (P = 0.04, P = 0.013, P = 0.01, respectively). TG and HDL-C showed no significant difference (P = 0.064, P = 0.336, respectively). The multivariate logistic regression model showed that age was a risk factor for the occurrence of endplate inflammation. In the group without underlying diseases, age, but not other indicators, was a risk factor for the occurrence of endplate inflammation (P < 0.01), In the group with underlying diseases, none of the patient indicators was directly related to the occurrence of endplate inflammation (P > 0.05). A nonlinear machine learning model was used to measure the contribution of each factor to the disease outcome and to analyze the effect between the top three contributing factors and the outcome variables. In patients without underlying diseases, the top three factors contributing to the severity grading of intervertebral disc degeneration were age (32.9%), high-density lipoproteins (20.7%), and triglycerides (11.8%). For the severity grading of facet joint degeneration, the top three contributing factors were age (27.7%), high-density lipoproteins (19.4%), and triglycerides (14.6%). For patients with underlying diseases, the top three factors contributing to intervertebral disc degeneration were age (25.4%), BMI (15.3%), and low-density lipoprotein/high-density lipoprotein ratio (13.9%). In terms of degree classification for facet joint degeneration, the top three contributing factors were age (17.5%), BMI (17.2%), and total cholesterol (16.7%). This study shows that age, high-density lipoprotein, and triglycerides affect the degree of degeneration in patients with symptomatic lumbar degeneration without underlying diseases. Age and BMI are two major factors affecting the severity of degeneration in patients with underlying diseases, and dyslipidemia is a secondary factor. However, there is no clear association between dyslipidemia and the occurrence of endplate inflammation in either group.

Development and Validation of a Novel Nomogram to Predict the Risk of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been a complex disorder resulted from genetic and environmental risk factors. The aim of this study was to identify the risk factors associated with IVDD in orthopaedic patients and develop a prediction model for predicting the risk of IVDD. A total of 309 patients were retrospectively included in the study and randomly divided into the training group and the validation group. The least absolute shrinkage and selection operator regression (LASSO) and the univariate logistic regression analysis were used to optimize factors selection for the IVDD risk model. Multivariable logistic regression analysis was used to establish a predicting nomogram model incorporating the factors. In addition, discrimination, calibration, and clinical usefulness of the nomogram model were evaluated via the C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Then, based on the results above, the relationship between IVDD and angiotensin II (AngII) level in peripheral blood was examined prospectively. The predictors of the nomogram include age, sex, hypertension, diabetes, gout, working posture, and exercising hours per week. The C-index values of the training and validation groups were 0.916 (95% CI, 0.876-0.956) and 0.949 (95% CI, 0.909-0.989), respectively, which indicated that the model displayed good discrimination. In addition, the area under the curve (AUC) values of the ROC curve of the training and the validation group were 0.815 (95% CI, 0.759-0.870) and 0.805 (95% CI, 0.718-0.892), respectively, revealing the satisfactory discrimination performance of the model. The prospective investigation showed that the average AngII level in the degenerated group (97.62 ± 44.02 pg/mL) was significantly higher than that in the nondegenerated group (52.91 ± 9.01 pg/mL) (p < 0.001). This present study explored the risk factors for IVDD and established a prediction model, which would effectively predict the risk of IVDD. In addition, based on the prediction model, AngII was revealed to be a potentially auxiliary clinical diagnostic marker for IVDD.

Significance of Immune-Related Genes in the Diagnosis and Classification of Intervertebral Disc Degeneration

Background With the extensive development of intervertebral disc degeneration (IDD) research, IDD has been found to be a complex disease associated with immune-related gene (IRGs) changes. Nonetheless, the roles of IRGs in IDD are unclear. Methods In our study, 11 IRGs were chosen using differential analysis between nondisc degeneration and degenerative patients from the GEO database. Then, we utilized a random forest (RF) model to screen six candidate IRGs to predict the risk of IDD. A nomogram was developed on the basis of six candidate IRGs, and DCA showed that patients could benefit from the nomogram. Based on the selected significant IRGs, a consensus clustering approach was used to differentiate disc degeneration patients into two immune patterns (immune cluster A and B). The PCA algorithm was constructed to compute immune scores for every sample, to quantify immune patterns. The immune scores of immune cluster B patients were higher than those of immune cluster A. Results Through differential expression analysis between healthy and IDD samples, 11 significant IRGs (CTSS, S100Z, STAT3, KLRK1, FPR1, C5AR2, RLN1, IFGR2, IL2RB, IL17RA, and IL6R) were recognized through significant IRGs. The “Reverse Cumulative Distribution of Residual” and “Boxplots of Residual” indicate that the RF model has minimal residuals. The majority of samples in the model have relatively small residuals, demonstrating that the model is better. Besides, the nomogram model was constructed based on importance and the IRGs with importance scores greater than 2 (FPR1, RLN1, S100Z, IFNGR2, KLRK1, and CTSS). The nomogram model revealed that decision-making based on an established model might be beneficial for IDD patients, and the predictive power of the nomogram model was significant. In addition, we identified two different immune cluster patterns (immune cluster A and immune cluster B) based on the 11 IRGs. We found that immune cluster A had significantly higher levels of MDSC, neutrophil, plasmacytoid dendritic cell, and type 17 T helper cell expression than immune cluster B. And we calculated the score for each sample to quantify the gene patterns. The patients in immune cluster B or gene cluster B had higher immune scores than those in immune cluster A or gene cluster A. Conclusion In conclusion, IRGs play an extremely significant role in the occurrence of IDD. Our study of immune patterns may guide the strategies of prevention and treatment for IDD in the future.

Vitamin D receptor gene polymorphisms and risk of intervertebral disc degeneration: An updated meta-analysis based on 23 studies.

Background:Numerous studies have investigated the associations between Vitamin D receptor (VDR) gene polymorphisms and risk of intervertebral disc degeneration but the results remain controversial. This study aimed to drive a more precise estimation of association between VDR gene polymorphisms and risk of intervertebral disc degeneration.Methods:PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on VDR gene polymorphisms and risk of intervertebral disc degeneration were searched. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive model.Results:Overall, 23 articles were included in the final meta-analysis. The subgroup analyses by ethnicity showed a significant association of VDR FokI mutation with disc degeneration risk in Caucasians (recessive model, OR with 95%CI 1.301, [1.041, 1.626]; additive model, OR with 95%CI 1.119, [1.006, 1.245]). The results of subgroup analyses by ethnicity showed a significant association of VDR TaqI mutation with disc degeneration risk in Asians but not in Caucasians. There was a significant association between VDR ApaI mutation and risk of disc degeneration and subgroup analyses by ethnicity showed a significant association in Caucasians and in Asians.Conclusions:In summary, VDR FokI polymorphisms was associated with disc degeneration risk among Caucasians but not Asians, VDR TaqI polymorphisms was associated with disc degeneration risk among Asians but not Caucasians, while VDR ApaI polymorphism was associated with disc degeneration risk among Asians and Caucasians.

Protective effect of estrogen receptors (ERα/β) against the intervertebral disc degeneration involves activating CCN5 via the promoter.

Due to the decrease of estrogen and estrogen receptor (ER) in postmenopausal women, they have a higher risk of intervertebral disc degeneration (IDD) than men. This study aims to explore how ERα and ERb interact with CCN5 and protect IDD. We used Chromatin immunoprecipitation (ChIP) and Luciferase reporter assay to determine whether the ERα/b protein binds to CCN5 promoter and activates its expression. We used TNF-α to induce nucleus pulposus (NP) cell degeneration to simulate the IDD process. The change of the expression of ERα/β and CCN5 was measured in the degenerated NP cells. To understand the function of ERα/β in the NP cells degeneration, we upregulated the ERα/b gene expression by vector transfection or 17b-estradiol (E2) stimulation. Besides, we also used the CCN5 gene-silenced NP cells by siRNA transfection as a comparison to determine the role of CCN5. We tested the cell proliferation and principal components of the extracellular matrix (ECM) to value the degree of NP cell degeneration. ERα and ERβ protein can bind to the same promoter regions of CCN5 and activate its expression, respectively. TNF-α degraded NP cells with a reduction of cell proliferation, collagen II, ACAN, ERα, ERβ, and CCN5 expression, and increased collagen I/III, and MMP-13 expression. Upregulated ERα or ERβ resulted in the maintains of CCN5 and alleviated the NP cell degeneration. Besides, 17β-E2 supplement increased the ERα, ERβ, and CCN5 expression, as well as stable NP cells phenotype. However, it was partly abolished by the silencing of CCN5. Upregulation of ERα and ERβ protects the NP cell degeneration during IDD through the activation of CCN5 by binding to its promoter.

Clinical observation of single-segment cervical adjacent segment disease treated with artificial cervical disc replacement

Objective: To investigate the clinical outcomes and radiographic results of artificial cervical disc replacement (ACDR) for cervical adjacent segment disease (ASD). Methods: The clinical data of 28 patients with single-segment cervical ASD treated with ACDR in Xi 'an Honghui Hospital from December 2013 to July 2016 were retrospectively analyzed. There were 19 males and 9 females with a mean age of (46±7) years (36-63 years). Preoperative, postoperative 1 month and postoperative 24 months of clinical and radiographic outcomes were recorded and compared. The clinical outcome mainly includes Japanese orthopedic association (JOA), Neck Disability Index (NDI%), Odom score and complications. Imaging assessment mainly included range of motion (ROM) of cervical spine, surgical segment ROM, Cobb angle of surgical segment, degree of adjacent disc degeneration, heterotopic ossification, and prosthesis related image parameters. Results: In terms of clinical outcome, the average JOA score was 12.7±1.5 before surgery, 14.0±1.0 one month after surgery, 15.8±0.9 24 months after surgery, and the improvement rate of JOA was 75%±19%. The mean NDI% was 27.0%±2.8% before surgery, 20.5%±1.6% one month after surgery, and 15.3%±2.8% 24 months after surgery; the difference before and after treatment was statistically significant (F=159.101, P<0.01). Twenty patients were classified with excellent Odom score and 8 patients with good Odom score at the final follow-up. The total ROM of cervical spine, operation segment ROM, operation segment Cobb angle were all improved significantly after the operation (F=4.633, 6.063, 26.952, all P<0.05). There was a statistical difference in Miyazaki classification between adjacent discs above ACDR and below the fusion segment 24 months after surgery (μ(c)=2.12, P=0.034). The incidence of heterotopic ossification was 14.3%. The results of displacement degree of prosthesis were as follow: coronal plane (0.30±0.11) mm, sagittal plane (0.28±0.10) mm; subsidence of the prosthesis: (0.27±0.09) mm. No prosthesis loosening was observed. Conclusions: The clinical outcome of revision of cervical ASD by ACDR is satisfactory. The risk of intervertebral disc degeneration in adjacent segments is significantly lower than that of ACDF due to the presence of certain motor function postoperatively.

A Meta-analysis Assessing the Association Between COL11A1 and GDF5 Genetic Variants and Intervertebral Disc Degeneration Susceptibility

Meta-analysis to collect relevant studies to assess the association between COL11A1 and GDF5 genetic variants and susceptibility to IDD. The aim of this study was to assess whether or not COL11A1 and GDF5 genetic variants were associated with susceptibility to IDD. IDD or LDH is a major public health problem. There have been several studies evaluating the relationship between COL11A1 and GDF5 genetic variants with risk of intervertebral disc degeneration (IDD). However, the studies were limited in discrete outcome and sample size, and some of the results were contradictory. We systematically searched the relevant publications in electronic databases. Eligible studies were included based on the defined criteria. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were received using STATA 15. Subgroup analysis, sensitivity analysis, publication bias, and the "Trim and fill" method were performed in the meta-analysis. A total of 3287 IDD cases and 5115 controls were incorporated into the meta-analysis. Our results demonstrated that COL11A1 rs1676486 was significantly associated with increased IDD susceptibility under all genetic models (allele model T vs. C: OR = 1.40, 95% CI 1.23-1.59, P = 0.000; homozygote model TT vs. CC: OR = 1.89, 95%CI 1.40-2.56, P = 0.000; dominant model TT+TC vs. CC: OR = 1.52, 95% CI 1.29-1.80, P = 0.000; recessive model TT vs. TC + CC: OR = 1.58, 95% CI 1.18-2.12, P = 0.002). However, GDF5 rs143383 was not (allele model T vs. C: OR = 1.15, 95% CI 0.91-1.44, P = 0.244; homozygote model TT vs. CC: OR = 1.22, 95% CI 0.75-2.00, P = 0.429; dominant model TT vs. CC+CT: OR = 1.22, 95% CI 0.95-1.57, P = 0.112; recessive model TC + TT vs. CC: OR = 1.12, 95% CI 0.73-1.73, P = 0.594). Subgroup analysis indicated ethnicity was not the source of heterogeneity. Sensitivity analysis, publication bias, and the "Trim and fill" method demonstrated the meta-analysis was of reliability. Our results suggested that COL11A1 rs1676486 was significantly associated with IDD and the T allele was a risky factor. However, GDF5 rs143383 was not. 1.

Downregulation of microRNA-129-5p increases the risk of intervertebral disc degeneration by promoting the apoptosis of nucleus pulposus cells via targeting BMP2.

miR-129-5p is implicated in many diseases, such as laryngeal cancer and breast cancer. In this study, we studied the mechanism underlying the role of BMP2 in intervertebral disc degeneration (IDD). We used a luciferase assay system to determine the relationship between BMP2 and miR-129-5 expression. In addition, Western blot and real-time PCR were used to confirm the regulatory relationship between miR-129-5p and its targets, while flow cytometry was used to evaluate the effect of miR-129-5p on the apoptosis of neural progenitor cells (NPCs). BMP2 was confirmed as a direct target of miR-129-5p. Furthermore, the expression of miR-129 was downregulated along with upregulated BMP2 expression in IDD patients. Meanwhile, BMP2 was validated as the target of miR-129-5p in cells transfected with miR-129-5p and BMP2 siRNA. Also, compared with NPCs transfected with blank/scramble controls or miR-129-5p inhibitors, the NPCs treated with miR-129-5p mimics or BMP2 siRNA exhibited evidently elevated viability and inhibited apoptosis. The data demonstrated that miR-129-5p was poorly expressed in IDD patients, and the dysregulation of miR-129-5p might contribute to the development of IDD by targeting BMP2 expression.

FokI as a genetic factor of intervertebral disc degeneration: A PRISMA-compliant systematic review of overlapping meta-analyses

The association of FokI (rs2228570), a polymorphism of the vitamin D receptor gene, with intervertebral disc degeneration (IDD) has been investigated in a multitude of studies. However, conflicting results of these studies led to emergence of several meta-analyses over the past few years. Despite the increased statistical power, these meta-analyses have failed to provide uniform and conclusive data on the relationship of FokI with IDD. The aim of this study was to present a comprehensive review based on the most up-to-date meta-analyses on the association of FokI with IDD. A comprehensive search of all major databases was conducted to identify meta-analyses investigating relation between FokI and IDD. No date or language restrictions were applied. The Jadad decision algorithm was utilized to evaluate included meta-analyses and identify the one providing the best evidence. A total of 7 meta-analyses (n = 2580 original patients), that included six to ten case control studies, analyzed the association of FokI polymorphism with IDD. The meta-analysis of the highest quality supported the notion that overall there is no statistically significant association between FokI polymorphism and IDD. However, the authors showed that Caucasians have a reduced risk of IDD and Hispanics have an increased risk of IDD in the dominant and dominant/homozygous/heterozygous models of FokI polymorphism. While currently there is no evidence of an association between FokI polymorphism and IDD in the general population, ethnic predisposition has been shown.

Association between GDF5 rs143383 genetic polymorphism and musculoskeletal degenerative diseases susceptibility: a meta-analysis

BackgroundSeveral studies have assessed the association between GDF5 rs143383 polymorphism and the susceptibility of musculoskeletal degenerative diseases, such as intervertebral disc degeneration (IDD) and osteoarthritis (OA), but the results are inconsistent. The aim of our study was to evaluate the association between them comprehensively.MethodsA systematical search was conducted on PubMed, Scopus, Web of Science (WOS), Embase, and the Cochrane Library databases updated to April 20, 2018. Eligible studies about polymorphisms in GDF5 gene and risk of IDD or OA were included. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized.ResultsFifteen studies with a total of 5915 cases and 12,252 controls were finally included in our study. Meta-analysis of GDF5 rs143383 polymorphism was statistically associated with increased risk of musculoskeletal degenerative diseases under each genetic model (allele model: OR = 1.32, 95% CI 1.19–1.48, P = 0.000; homozygote model: OR = 1.80, 95%CI 1.49–2.16, P = 0.000; heterozygote model: OR = 1.37, 95%CI 1.21–1.55, P = 0.000; dominant model: OR = 1.56, 95%CI 1.39–1.75, P = 0.000; recessive model: OR = 1.39, 95%CI 1.20–1.60, P = 0.000). Stratified analyses based on disease type showed a significant association between the GDF5 rs143383 polymorphism and increased risk of IDD and OA under all genetic models studied. When stratified with ethnicity, pooled outcomes revealed that this polymorphism was significantly related with increased risk of musculoskeletal degenerative diseases in both Asian and Caucasian populations under all genetic models studied.ConclusionsThe present study suggested that GDF5 rs143383 polymorphism was significantly associated with susceptibility to musculoskeletal degenerative diseases.

Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Risk of Intervertebral Disc Degeneration in Chinese Han Population: A Case Control Study.

BackgroundThe present study aimed to evaluate whether the fat mass and obesity-associated (FTO) gene polymorphisms are associated with risk of intervertebral disc degeneration (IDD) in a largest Chinese Han population.Material/MethodsThere were 502 IDD patients and 497 healthy controls enrolled in this study. Nineteen single nucleotide polymorphisms (SNPs) in the FTO gene were tested using the Sequenom MassARRAY platform. The Hardy-Weinberg equilibrium test, followed by allelic, genotypic, haplotypic association, and SNP interaction analyses were used for SNP evaluation. The Genotype-Tissue Expression (GTEx) database was used to evaluate expression quantitative trait loci (eQTL) value of polymorphism. Spearman rank correlation and logistic regression analyses were used for assessing the internal relation between genotypic changes and the risk of IDD.ResultsSeventeen SNPs survived the Hardy-Weinberg equilibrium test. Allelic analysis showed that allele T of SNP rs1121980 was a risk allele. Haplotypic and SNP interaction analyses suggested that 2 haplotypes and 5 SNP combinations were associated with the predisposition of IDD respectively. GTEx database revealed that the SNP rs1121980 might interfere with the expression of the FTO gene in the muscle-skeletal system. Through clinical statistics analysis, the different genotypes of rs1121980 can present different disease severity of IDD.ConclusionsOur study suggests that rs1121980 can become a biomarker for the screening and prognosis of IDD. The 2 haplotype blocks and 5 SNP-SNP combinations that we discovered might be indicative of the onset of IDD. Therefore, our study might serve as evidence for future IDD molecular diagnosis.

Association of interleukin 1 gene polymorphism with intervertebral disc degeneration risk in the Chinese Han population.

Intervertebral disc degeneration (IDD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Interleukin-1 α (IL-1α) was thought to be involved in the pathogenesis of disc degeneration by increasing the production of extracellular matrix degradation enzymes and by inhibiting extracellular matrix synthesis. IL-1α may provide insight about the etiology of IDD. We performed a hospital-based case–control study involving 200 IDD patients and 200 controls in the Chinese Han population. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ Kit. Our study indicated that IL-1α -899C/T polymorphism could increase the risk of IDD under the homozygous, recessive, and allelic models. Subsequently, we validated this significant association by a meta-analysis. Stratification analysis of ethnicity in this meta-analysis also obtained a significant association among Asians and Caucasians. In conclusion, the present study finds that IL-1α -899C/T polymorphism is associated with the risk of IDD. Larger studies with more diverse ethnic populations are needed to confirm these results.