Causal relationship between systemic circulatory inflammatory regulators and intervertebral disc degeneration: A bidirectional 2-sample Mendelian randomization study.

In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1ß (OR = 0.956, 95% CI: -0.08 to -0.006; P = .02) and IFN-G (OR = 0.915, 95% CI: -0.16 to -0.02; P = .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (OR = 0.967, 95% CI: -0.063 to -0.004; P = .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.

Nucleotide polymorphism-based study utilizes human plasma liposomes to discover potential therapeutic targets for intervertebral disc disease.

Background: While intervertebral disc degeneration (IVDD) is crucial in numerous spinally related illnesses and is common among the elderly, the complete understanding of its pathogenic mechanisms is still an area of ongoing study. In recent years, it has revealed that liposomes are crucial in the initiation and progression of IVDD. However, their intrinsic mediators and related mechanisms remain unclear. With the development of genomics, an increasing amount of data points to the contribution of genetics in the etiology of disease. Accordingly, this study explored the causality between liposomes and IVDD by Mendelian randomization (MR) analysis and deeply investigated the intermediary roles of undetected metabolites. Methods: According to MR analysis, 179 liposomes and 1400 metabolites were evaluated for their causal association with IVDD. Single nucleotide polymorphisms (SNPs) are strongly associated with the concentrations of liposomes and metabolites. Consequently, they were employed as instrumental variables (IVs) to deduce if they constituted risk elements or protective elements for IVDD. Furthermore, mediation analysis was conducted to pinpoint possible metabolic mediators that link liposomes to IVDD. The inverse variance weighting (IVW) was the main analytical technique. Various confidence tests in the causality estimates were performed, including consistency, heterogeneity, pleiotropy, and sensitivity analyses. Inverse MR analysis was also utilized to estimate potential reverse causality. Results: MR analysis identified 13 liposomes and 79 metabolites markedly relevant to IVDD. Moreover, the mediation analysis was carried out by choosing the liposome, specifically the triacylglycerol (48:2) levels, which were found to be most notably associated with an increased risk of IVDD. In all, three metabolite-associated mediators were identified (3-methylcytidine levels, inosine 5'-monophosphate (IMP) to phosphate ratio, and adenosine 5'-diphosphate (ADP) to glycine ratio). Conclusion: The analysis's findings suggested possible causal connections between liposomes, metabolites, and IVDD, which could act as both forecast and prognosis clinical indicators, thereby aiding in the exploration of the pathogenesis behind IVDD.

Serum periostin levels correlate with severity of intervertebral disc degeneration.

PURPOSE: Periostin, an extracellular matrix protein closely related to mechanical stress, inflammation, and ageing, has been implicated in intervertebral disc degeneration (IVDD) in basic research. However, it has not been examined in clinical cases. This study aimed to evaluate the association between IVDD severity and serum periostin concentration as well as to analyse potential associations between IVDD and clinical and demographic factors. METHODS: This retrospective cohort study included 198 patients who underwent lumbar disc herniation and lumbar canal stenosis between January 2020 and December 2022. The severity of IVDD was evaluated using the Pfirrmann grading, whereas serum periostin levels were measured using ELISA kits. Clinical demographics, including age, sex, body mass index, comorbidities, psoas muscle index, and spinal disease, were also recorded. RESULTS: This study demonstrated a significant correlation between high serum periostin levels and IVDD severity, as indicated by a high cumulative Pfirrmann score. Serum periostin levels were identified as an independent risk factor for IVDD in a multivariate regression model. Correlation analysis showed a correlation between periostin levels and Pfirrmann grade at each lumbar level (ρ = 0.458-0.550, p < 0.001) and a strong correlation with cumulative Pfirrmann score (ρ = 0.690, p < 0.001). CONCLUSION: The higher the serum periostin level, the higher the cumulative Pfirrmann score. Multivariate analysis showed that serum periostin was an independent risk factor for IVDD. Periostin levels may be a clinically suitable and useful biomarker for diagnosing IVDD, estimating disease progression and activity, providing prognostic information, and evaluating treatment options.

Evidence of MRI image features and inflammatory biomarkers association with low back pain in patients with lumbar disc herniation.

BACKGROUND CONTEXT: While MRI image features and inflammatory biomarkers are frequently used for guiding treatment decisions in patients with lumbar disc herniation (LDH) and low back pain (LBP), our understanding of the connections between these features and LBP remains incomplete. There is a growing interest in the potential significance of MRI image features and inflammatory biomarkers, both for quantification and as emerging therapeutic tools for LBP. PURPOSE: To investigate the evidence supporting MRI image features and inflammatory biomarkers as predictors of LBP and to determine their relationship with pain intensity. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: All consecutive patients with LDH who underwent discectomy surgery at our institution from February 2020 to June 2023 at the author's institution were included. OUTCOME MEASURES: MRI image features in discogenic, osseous, facetogenic, and paraspinal muscles, as well as inflammatory biomarkers in serum (including CRP (C-reactive protein), ESR (erythrocyte sedimentation rate), PCT (procalcitonin), TNF (tumor necrosis factor), interleukin-1 beta (IL-1ß), and IL-6), and paraspinal muscles (including TNF, IL-1ß, IL-6, IL-10, and transforming growth factor beta 1 (TGF-ß1)). METHODS: A series of continuous patients diagnosed with LDH were categorized into acute LBP (<12 weeks), chronic LBP (≥12 weeks), and nonLBP groups. MRI image features and inflammatory biomarkers relation to pain intensity was assessed using the independent t-test, Chi-squared tests, Spearman rank correlation coefficient, and logistic regression test. RESULTS: Compared to the nonLBP group, the chronic LBP group exhibited a higher incidence of intervertebral disc (IVD) degeneration (≥ grade 3) and high-fat infiltration in paraspinal muscles, alongside a significant reduction in the cross-sectional area (CSA) and fatty degeneration of the multifidus muscle. Furthermore, there was a greater expression of IL-6 in serum and TNF in paraspinal muscles in the chronic LBP group and a greater expression of CRP and IL-6 in serum and TNF in paraspinal muscles in the acute LBP group. CSA and fatty degeneration of multifidus muscle were moderately negatively correlated with chronic LBP scores. The expression of TNF and IL-6 in serum and the expression of TNF in the multifidus muscle were moderately correlated with preoperative LBP. IVD degeneration and high-fat infiltration were identified as risk factors for chronic LBP. CONCLUSION: The results provide evidence that IVD degeneration, high-fat infiltration, and the reduction of CSA in paraspinal muscles were associated with the development of chronic LBP in patients with LDH, and these associations are linked to inflammatory regulation. This deepens our understanding of the etiology and pathophysiology of LBP, potentially leading to improved patient stratification and more targeted interventions.

Increase in serum nerve growth factor but not intervertebral disc degeneration following whole-body vibration in rats.

BACKGROUND: Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration. METHODS: Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration. FINDINGS: The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect. INTERPRETATION: This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.

Identification of Characteristic Genes in Whole Blood of Intervertebral Disc Degeneration Patients by Weighted Gene Coexpression Network Analysis (WGCNA).

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. However, to date, the molecular mechanism of the IDD remains unclear. Gene expression profiles and clinical traits were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, weighted gene coexpression network analysis (WGCNA) was used to screen IDD-related genes. Moreover, least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine (SVM) algorithms were used to identify characteristic genes. Furthermore, we further investigated the immune landscape by the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and the correlations between key characteristic genes and infiltrating immune cells. Finally, a competing endogenous RNA (ceRNA) network was established to show the regulatory mechanisms of characteristic genes. A total of 2458 genes were identified by WGCNA, and 48 of them were disordered. After overlapping the genes obtained by LASSO and SVM-RFE algorithms, genes including LINC01347, ASAP1-IT1, lnc-SEPT7L-1, B3GNT8, CHRNB3, CLEC4F, LOC102724000, SERINC2, and LOC102723649 were identified as characteristic genes of IDD. Moreover, differential analysis further identified ASAP1-IT1 and SERINC2 as key characteristic genes. Furthermore, we found that the expression of both ASAP1-IT1 and SERINC2 was related to the proportions of T cells gamma delta and Neutrophils. Finally, a ceRNA network was established to show the regulatory mechanisms of ASAP1-IT1 and SERINC2. In conclusion, the present study identified ASAP1-IT1 and SERINC2 as the key characteristic genes of IDD through integrative bioinformatic analyses, which may contribute to the diagnosis and treatment of IDD.

The Dual Effect of Abnormal Serum Uric Acid on Intervertebral Disc Degeneration.

An abnormal serum uric acid (SUA) level is associated with many diseases. To our knowledge, there is no research on the association between SUA and intervertebral disc degeneration (IDD). The purpose of this study was to determine the relationship between SUA and IDD. From June 2011 to July 2020, 691 patients undergoing surgery for lumbar disc herniation (LDH) were included in the LDH group, and 684 patients who underwent endoscopic surgery for knee trauma were included in the non-LDH group. We examined the baseline characteristics of all these patients and divided the SUA level into 10 groups according to the percentiles in males, females, and the total population. Subsequently, the relationship between the SUA level and IDD was further analyzed. There was no statistically significant difference in the baseline characteristics of the two groups (p > 0.05). Among the 10 groups, the LDH rate was higher at both lower and higher SUA levels. In multiple logistic regression analysis, after adjustment for age, sex, body mass index, smoking, and drinking, when the SUA level was <20% or >80%, compared with 60-80%, the odds ratio (OR) and 95% confidence interval (CI) of LDH of the total population were 1.821 (1.125-2.946) and 1.701 (1.186-2.438), respectively, and in the males, they were 1.922 (1.169-3.161) and 2.800 (1.766, 4.439), respectively. In females, when the SUA was <20%, there was a higher LDH rate (OR = 1.951, 95% CI 1.091-3.486). The present study suggests that there is a U-shaped relationship between SUA and IDD, being particularly prominent among male. Lower and higher SUA level may be risk factors for IDD.

Lower Plasma Melatonin in the Intervertebral Disk Degeneration Patients Was Associated with Increased Proinflammatory Cytokines.

BACKGROUND: Intervertebral disc degeneration (IDD) was considered to be the pathological basis of intervertebral disc herniation (IDH). However, the plasma melatonin in the IDD cases and healthy controls remained unclear. METHODS: In this case-control study, a total of 71 IDD cases and 54 healthy controls were enrolled between April 2020 and August 2020. The diagnostic effect of plasma melatonin for IDD was detected using receiver operating characteristic curve. The correlations between two continuous variables were detected with the Pearson linear analyses. RESULTS: It was found that lower melatonin concentration was detected in the IDD cases (1.906 ± 1.041 vs 3.072 ± 0.511 pg/mL, P<0.001). Through receiver operating characteristic curve analyses, it was found that plasma melatonin could be used as a diagnostic biomarker for IDD (area under curve=0.808, P<0.001). In advanced correlation analyses, it was found that plasma melatonin concentration was negatively associated with the age, symptom durations, IDD disease severity and proinflammatory factors, including IL-6 and TNF-α concentrations (P<0.05). Comparing with the higher melatonin groups, significantly increased IL-6 (0.601 ± 0.085 vs 0.507 ± 0.167 pg/mL, P=0.028) and TNF-α (3.022 ± 0.286 vs 2.353 ± 0.641, P<0.001) were detected in the patients with lower melatonin concentration. CONCLUSION: The plasma melatonin concentration was significantly decreased in the IDD cases and plasma melatonin could be used as a diagnostic biomarker for IDD. Lower plasma melatonin was associated with longer disease durations, elevated disease severity and higher inflammatory cytokines levels in IDD patients.

Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population.

The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.

Expressions of IL-12 and its receptors in patients with lumbar disc herniation and their relationship with clinical efficacy.

This study aimed to explore the expressions of interleukin-12 (IL-12) and its receptors IL-23R and IL12RB2 in patients with lumbar disc herniation (LDH) before and after treatment and their relationship with clinical efficacy. A total of 172 LDH patients undergoing surgical treatment in Wuhan Third Hospital, Tongren Hospital of Wuhan University were enrolled as the study group, and 170 healthy subjects as the control group. 5 mL of fasting venous blood was taken before surgery (T0), 1 d (T1), 3 d (T2), 5 d (T3) and 7 d (T4) after treatment respectively. The concentrations of IL-12, IL-23R and IL12RB2 in the two groups were detected, and the correlation between them and the treatment duration and clinical efficacy was analyzed. The study group showed significantly higher serum IL-12, IL-23R and IL12RB2 than the control group before treatment (P < 0.001). In the study group, IL-12, IL-23R and IL-12RB2 were the lowest at T4 (P < 0.001), followed by T3 (P < 0.001). There was no significant difference in IL-23R at T1 and T0 (P > 0.050), and in IL12RB2 at T1 and T2 (P > 0.050). Spearman rank correlation showed that IL-12, IL-23R, IL12RB2 were negatively correlated with treatment duration in the study group (P < 0.001), and were positively correlated with clinical efficacy (P < 0.001). In conclusion, the concentrations of serum IL-12, IL-23R and IL12RB2 in LDH patients are significantly higher than those in normal controls. Moreover, the concentrations are closely related to the rehabilitation of patients and are expected to become therapeutic targets for LDH.

Relationship of lumbar disc degeneration with hemoglobin value and smoking.

BACKGROUND/OBJECTIVE: Although a number of studies report an important effect of smoking on disc degeneration and herniation, others did not identify such a relationship. The purpose of this study was to assess the relationship of lumbar disc degeneration with hemoglobin value and smoking. METHODS: The study included 200 adult patients who presented to the neurosurgery polyclinic with a complaint of back pain. Smoking habits were classified as "smoking for more than 10 years", "smoking for less than 10 years", and "not smoking". Lumbar disc degeneration was classified on modified Pfirrmann score according to lumbar MR images. Degeneration level was compared according to smoking group on Kruskal-Wallis test. The relationship between hemoglobin value and disc degeneration according to smoking group was assessed on the Spearman correlation coefficient. RESULTS: Disc degeneration values were significantly different between groups in L5-S1, L4-L5 and L3-L4 (P=0.018, P=0.012, P=0.038). Degeneration levels in L5-S1 in those who did not smoke were significantly lower than in those who smoked for both less and more than 10 years (P=0.048, P=0.022). No significant differences were found in degeneration level between those who smoked for more versus less than 10 years. For L3-L4 degeneration, there was a significant relationship with hemoglobin value in the group that did not smoke and in the group that smoked for more than 10 years (r=-0.395; P=0.009, r=0.329; P=0.018). CONCLUSION: This study found that, when risk factors such as systemic disease, heavy working conditions, obesity, trauma and family history were excluded, smoking increased lumbar disc degeneration. In addition, chronic smoking was found to increase hemoglobin values.

Influences of circulatory factors on intervertebral disc aging phenotype.

Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.

High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress.

Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. However, how DM affects annulus fibrosus (AF) biology remains unclear. The present study was aimed to investigate the effects and mechanism of high glucose on AF cell biology. Rat AF cells were cultured in baseline medium and culture medium with 0.2 M glucose. The inhibitor 4-PBA was added along with the high glucose culture medium to study the role of endoplasmic reticulum (ER) stress in this process. Compared with the control cells, high glucose significantly increased cell apoptosis ratio and caspase-3/9 activity, up-regulated mRNA/protein expression of Bax and caspase-3/cleaved caspase-3, but down-regulated mRNA/protein expression of Bcl-2. Moreover, high glucose increased mRNA and protein expression of CHOP, ATF-6 and GRP78. However, once ER stress was inhibited by the inhibitor 4-PBA in the high glucose group, cell apoptosis ratio and caspase-3/9 activity were decreased, mRNA/protein expression of Bax and caspase-3/cleaved caspase-3 was down-regulated, but mRNA/protein expression of Bcl-2 was up-regulated. In conclusion, high glucose condition can promote AF cell apoptosis through inducing ER stress. The present study helps us understand the mechanism of disc degeneration in DM patients.

Chemerin facilitates intervertebral disc degeneration via TLR4 and CMKLR1 and activation of NF-kB signaling pathway.

Now days, obesity is a major risk factor for intervertebral disc degeneration (IDD). However, adipokine, such as chemerin is a novel cytokine, which is secreted by adipose tissue, and are thought to be played major roles in various degenerative diseases. Obese individuals are known to have high concentration of serum chemerin. Our purpose was to study whether chemerin acts as a biochemical relationship between obesity, and IDD. In this study, we found that the expression level of chemerin was significantly increased in the human degenerated nucleus pulposus (NP) tissues, and had higher level in the obese people than the normal people. Chemerin significantly increased the inflammatory mediator level, contributing to ECM degradation in nucleus pulposus cells (NPCs). Furthermore, chemerin overexpression aggravates the puncture-induced IVDD progression in rats, while knockdown CMKLR1 reverses IVDD progression. Chemerin activates the NF-kB signaling pathway via its receptors CMKLR1, and TLR4 to release inflammatory mediators, which cause matrix degradation, and cell aging. These findings generally provide novel evidence supporting the causative role of obesity in IDD, which is essentially important to literally develop novel preventative or generally therapeutic treatment in the disc degenerative disorders.

Extreme lateral interbody fusion and percutaneous pedicle screw fixation in the minimally invasive treatment of thoracic tuberculosis.

OBJECTIVE: As a minimally invasive intervertebral fusion technique popularized in recent years, extreme lateral interbody fusion (XLIF) has various advantages. In this study, we describe the application and efficacy of XLIF for the treatment of thoracic tuberculosis (TB), as this may be an emerging treatment option for thoracic TB in the future. METHODS: We present the case of a 75-year-old man who had suffered from chest and back pain for 1 month. Imaging studies showed destruction of the T12 and L1 vertebral bodies and the T12-L1 intervertebral disc, accompanied by formation of a paravertebral abscess. After 2 weeks of standard anti-TB treatment, the patient underwent debridement of the lesions, XLIF, and percutaneous pedicle screw fixation. RESULTS: The patient's chest and back pain were significantly alleviated after the operation. The patient recovered well, and as of the most recent follow-up had no obvious limitation in thoracolumbar spine function. CONCLUSIONS: XLIF combined with percutaneous pedicle screw fixation for the treatment of thoracic TB can allow for TB lesion debridement, discectomy, and interbody fusion under direct visualization, and can effectively improve patient prognosis.

[Serum biomarkers in acute low back pain and sciatica]. / Szérumbiomarkerek akut lumbalis-lumbosacralis fájdalomban.

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

BACKGROUND: It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD. METHODS: A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were used to investigate gene expression levels. Cell transfections were carried out to analyze gene interactions. The diagnostic value of lncRNA MAGI2-AS3 for IDD was assessed by ROC curve analysis. RESULTS: The expression levels of plasma lncRNA MAGI2-AS3 were lower in IDD patients compared to that in the control group. Down-regulation of lncRNA MAGI2-AS3 effectively distinguished IDD patients from the control group. The expression levels of plasma lncRNA MAGI2-AS3 were significantly increased after the treatments. Over-expression of lncRNA MAGI2-AS3 inhibited the expression of FasL, while the silencing of lncRNA MAGI2-AS3 promoted the expression of FasL in nucleus pulposus (NP) cells. CONCLUSIONS: Therefore, lncRNA MAGI2-AS3 is down-regulated in IDD and participates in the regulation of FasL expression in nucleus pulposus (NP) cells.

Effect of subcutaneous needling on visual analogue scale, IgG and IgM in patients with lumbar disc herniation: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Lumbar disc herniation (LDH) is a disease commonly seen in clinical practice. In the majority of such patients presenting in clinic, the symptoms can be relieved or even abolished after non-surgical treatment. Floating needle therapy has attracted considerable attention as a promising non-surgical technique to treat LDH, as demonstrated in previous studies. The purpose of the present study was to evaluate the outcomes of patients treated using this therapy in a single blind and randomized controlled trial by recording patient report questionnaires and objective test data, and to explore the feasibility and preliminary effects of floating needle therapy for patients with LDH. METHODS: A total of 80 patients who fulfilled the inclusion criteria were randomly divided into a Fu's subcutaneous needling (FSN) group and an acupuncture group then treated in accordance with procedures appropriate for a single blind and randomized controlled trial. The FSN group received 12 FSN therapy sessions over a 3-week period, and the acupuncture group received acupuncture therapy at specified points using acupuncture needles. The principal measurements were scored using the visual analogue scale (VAS), Japanese Orthopedic Association (JOA) Score, and Oswestry disability index (ODI) before and 3 weeks after treatment. Secondary measurements included immune function IgG and IgM measurements performed at the same time and adverse reactions during treatment. RESULTS: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. CONCLUSIONS: This study will explore the feasibility and preliminary effects of floating needle therapy for the treatment of patients with LDH. REGISTRATION: PROSPERO (registration number ChiCTR1900024045).

Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency.

BACKGROUND: The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. METHODS: Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. RESULTS: The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). CONCLUSIONS: T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project.

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006-2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027-1037, 2020.