Background/Objectives: Additional lateral fixation is a method with the potential to redistribute cage loading during oblique lumbar interbody fusion (OLIF). However, its biomechanical effects remain poorly understood. This study aimed to compare the mechanical responses of the lumbar spine following OLIF, both with and without additional lateral fixation, using a finite element (FE) analysis. Methods: An FE lumbar model with an OLIF cage at the L4-L5 levels was developed. A lateral fixation system comprising screws and a rod was incorporated to redistribute the cage loading and enhance spinal stability. Two OLIF cage positions-centered and at an oblique angle-were compared. Results: The additional lateral fixation reduced cage loading by 70% (409 to 123 N) and 72% (411 to 114 N) for the centered and oblique cage positions, respectively. Without lateral fixation, the peak equivalent stress on the cage during extension increased threefold (66 to 198 MPa) for the oblique position compared with that for the centered position. Conclusions: An additional lateral screw-rod fixation system is suggested as a complementary approach to the OLIF technique to mitigate endplate loading and pressure.

Intervertebral disc degeneration (IVDD) is a significant cause of global disability, reducing labor productivity, increasing the burden on public health, and affecting socio-economic well-being. Currently, there is a lack of recognized clinical approaches for molecular classification and precision therapy.

Chondrocyte differentiation and prognosis-related genes were extracted from single-cell RNA sequencing and multi-omics data in the Gene Expression Omnibus (GEO) database through chondrocyte trajectory analysis and non-parametric tests. Subsequently, a precise IVDD risk stratification system was developed using ConsensusClusterPlus analysis. The clinical significance of molecular typing was demonstrated through case-control trials involving IVDD patients. Specific inhibitors of molecular typing were predicted using the pRRophetic package in R language and then validated in vitro.

A stratified model for IVDD, considering chondrocyte differentiation and demonstrating high clinical relevance, was developed using a set of 44 chondrocyte fate genes. Extensive analyses of multi-omics data confirmed the clinical relevance of this model, indicating that cases in the High Chondrocyte Scoring Classification (HCSC) group had the most favorable prognosis, whereas those in the Low Chondrocyte Scoring Classification (LCSC) group had the worst prognosis. Additionally, clinical case-control studies provided evidence of the utility of IVDD molecular typing in translational medicine. A gene expression-based molecular typing approach was used to create a matrix identifying potential inhibitors specific to each IVDD subtype. In vitro experiments revealed that gefitinib, a drug designed for LCSC, not only had protective effects on chondrocytes but also could induce the conversion of LCSC into the HCSC subgroup. Therefore, IVDD molecular typing played a critical role in assisting clinicians with risk stratification and enabling personalized treatment decisions.

The results of the study have provided a comprehensive and clinically relevant molecular typing for IVDD, involving a precise stratification system that offers a new opportunity for customizing personalized treatments for IVDD.

Chronic low back pain (LBP), often correlated with intervertebral disc degeneration, is a leading source of disability worldwide yet remains poorly understood. Current treatments often fail to provide sustained relief, highlighting the need to better understand the mechanisms driving discogenic LBP. During disc degeneration, the extracellular matrix degrades, allowing nociceptive nerve fibers to innervate previously aneural disc regions. Persistent mechanical and inflammatory stimulation of nociceptors can induce plastic changes within dorsal root ganglia (DRG) neurons, characterized by altered gene expression, enhanced excitability, and lowered activation thresholds. Although these transcriptional changes have been described in other pain states, including osteoarthritis, they remain underexplored in discogenic LBP. To address this gap, this study represents the first application of comprehensive single-nuclei RNA sequencing of DRG neurons in a rat model of chronic discogenic LBP. Eighteen distinct DRG subpopulations were identified and mapped to existing mouse and cross-species atlases revealing strong similarities in neuronal populations with the mouse. Differential expression analysis revealed increased expression of pain-associated genes, including Scn9a and Piezo2, and neuroinflammatory mediators such as Fstl1 and Ngfr, in LBP animals. Axial hypersensitivity, measured using grip strength, significantly correlated with increased expression of Scn9a, Fstl1, and Ngfr, which suggests their role in maintaining axial hypersensitivity in this model. These findings establish a relationship between DRG transcriptomic changes and axial hypersensitivity in a discogenic LBP model, identifying potential molecular targets for non-opioid treatments and advancing understanding of discogenic LBP mechanisms.

The purpose of this study was to boost the therapeutic effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) by overexpressing the gene TSG-6 through CRISPR activation, and assess the biological activity of EVs from these modified MSCs in vitro on human intervertebral disc (IVD) cells.

An immortalized human MSC line was transduced with a CRISPR activation lentivirus system targeting TSG-6. MSC-EVs were harvested by ultracentrifugation and particle number/size distribution was determined by nanoparticle tracking analysis. The efficiency of transduction activation was assessed by analyzing gene and protein expression. EV proteomic contents were analyzed by mass spectrometry. Human IVD cells from patients undergoing spinal surgery were isolated, expanded, exposed to IL-1β pre-stimulation and co-treated with MSC-EVs.

MSC-EVs presented size distribution, morphology, and molecular markers consistent with common EV characteristics. The expression level of TSG-6 was significantly higher (> 800 fold) in transduced MSCs relative to controls. Protein analysis of MSCs and EVs showed higher protein expression of TSG-6 in CRISPR activated samples than controls. Proteomics of EVs identified 35 proteins (including TSG-6) that were differentially expressed in TSG-6 activated EVs vs control EVs. EV co-Treatment of IL-1β pre-Stimulated IVD cells resulted in a significant downregulation of IL-8 and COX-2.

We successfully generated an MSC line overexpressing TSG-6. Furthermore, we show that EVs isolated from these modified MSCs have the potential to attenuate the pro-inflammatory gene expression in IVD cells. This genomic engineering approach hence holds promise for boosting the therapeutic effects of EVs.

The online version contains supplementary material available at 10.1007/s12195-025-00843-4.

The objective of the current study was to investigate the correlation between polymorphisms in extracellular matrix-degrading enzymes and the risk of intervertebral disc degeneration (IDD) diseases.

The databases PubMed, Embase, and Cochrane Database were systematically queried from the inception until March 2023 to ascertain studies that meet the eligibility criteria. Utilizing a standardized data collection form to extract data from individual studies. The data were quantified using odds ratio (OR) along with its corresponding 95% confidence interval (95% CI), following an allelic model of inheritance.

The study included a total of nine studies and indicated that the presence of rs17576 in the MMP9 gene was significantly associated with an increased risk of IDD diseases (GG: 1.30, 95% CI [1.09-1.55], p = 0.004). The presence of other polymorphisms in extracellular matrix-degrading enzymes did not exhibit a significant association with the susceptibility to IDD.

The current study demonstrated a noteworthy correlation between the GG genotype of MMP-9 rs17576 and susceptibility to IDD. The available evidence is insufficient to substantiate the correlation between other extracellular matrix-degrading enzymes and susceptibility to IDD. The constraints of this analysis necessitate further research involving larger sample sizes across diverse ethnicities to provide a comprehensive understanding of the true impact of these polymorphisms on susceptibility to IDD.

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.

A growing body of research indicates a correlation between occupational exposure, particularly among individuals in driving-related occupations, and the incidence of low back pain (LBP).

Databases were systematically searched, including PubMed, Embase, Web of Science, Cochrane Library, and SinoMed, from their inception through December 2023 for relevant studies of the prevalence and risk factors of LBP among professional drivers. Subsequent meta-analyses were performed utilizing Stata 17.0 and RevMan 5.4 software, while risk factor indicators were assessed using the Grading of Recommendations, Assessment, Development and Evaluation evidence quality grading system.

A systematic review and meta-analysis comprising 19 studies involving 7,723 patients indicated that the incidence of LBP among drivers was 39% (95% confidence interval [CI] 0.20-0.57) in the past 7 days and 53% (95% CI 0.43-0.63) in the past 12 months. A subgroup analysis revealed a prevalence of 48% (95% CI 0.33-0.64) in 2005-2015 and 56% (95% CI 0.42-0.70) in 2016-2023. Among the identified factors, robust evidence highlighted age ≥ 41 years (odds ratio [OR] = 2.10; 95% CI 1.36-3.24; P = 0.0008), alcohol consumption (OR = 1.75; 95% CI 1.31-2.34; P = 0.0001), sleeping < 6 h/night (OR = 1.60; 95% CI 1.13-2.24; P = 0.007), uncomfortable seating (OR = 1.71; 95% CI 1.23-2.36; P = 0.001), improper driving posture (OR = 2.37; 95% CI 1.91-2.94; P < 0.00001), and manual handling (OR = 2.23; 95% CI 1.72-2.88; P < 0.00001) as significant risk factors for LBP. There was moderate evidence of a lack of exercise (OR = 1.78; 95% CI 1.37-2.31; P < 0.0001), working > 10 h/day (OR = 2.49; 95% CI 1.89-3.28; P < 0.00001), > 5 years' driving experience (OR = 2.12; 95% CI 1.66-2.69; P < 0.00001), a lack of back support (OR = 1.81; 95% CI 1.25-2.62; P = 0.002), high work-related pressure (OR = 2.04; 95% CI 1.59-2.61; P < 0.00001), and job dissatisfaction (OR = 1.57; 95% CI 1.23-2.01; P = 0.0003) as moderate risk factors. There was no evidence of body mass index or smoking as risk factors for LBP among professional drivers.

The current evidence indicates an increasing annual trend in the prevalence of LBP among professional drivers. Factors including age ≥ 41 years, alcohol consumption, and sleeping < 6 h/night were among the 12 influential factors contributing to LBP in professional drivers. Enhancing awareness of these factors and formulating targeted preventive strategies may be beneficial.

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.

Background: Standard oblique cages cannot cover endplates side-to-side, which is an important biomechanical factor for reducing the risk of cage subsidence and for restoring correct segmental lordosis. The aim of this study is to evaluate the radiological and clinical results of a new oblique lumbar interbody fusion (OLIF) axially expandable cage. Methods: This is a prospective observational case-control study. From March 2018 to June 2020, 28 consecutive patients with lumbar degenerative disease underwent an ATP approach, with the insertion of a new axially expandable cage, which was used as a stand-alone procedure or followed by posterior percutaneous pedicle fixation. Results: Twenty-eight patients in both groups met the inclusion criteria. The mean follow-up time was 31.2 months (range of 13-37). The clinical results were not significantly different, although in the control group, two major intraoperative complications were recorded, and slight improvements in ODI and SF-36 scores were observed in the study group. The radiological results showed a less frequent incidence of subsidence and a higher rate of fusion in the study group compared to controls. Conclusions: The axially expandable oblique cage for lumbar inter body fusion, specifically designed for the ATP approach, represents an innovation and a technical improvement. The insertion and the axial expansion technique are safe and easy. The large footprint could obtain solid and effective arthrodesis, potentially reducing the risk of subsidence.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient's own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.

Retrospective radiological examination (X-ray and MRI) aims to investigate the diagnostic value of various methods of measurement with regard to the determination of the intervertebral disc heights of the lumbar spine.

Of 130 patients without detectable damage to the intervertebral discs, the X-ray and MRI images of the lumbar spine were evaluated. The measurements were made either in the center line (Hurxthal) or in the 2-point method according to Dabbs or in the 3-point method according to Fyllos.

The average intervertebral disc height for all measured segments was 8.8 mm (SD 1.4 mm). In the Hurxthal measurement, the significantly (p < 0.001) highest values were measured with an average of 9.1 mm (SD 1.3 mm). The average readings for the Fyllos method were 7.5 mm (SD 1.2 mm) and according to Dabbs 6.7 mm (SD 1.2 mm). The measured values of Observer I were on average 1.2 mm (SD 0.3 mm) smaller than those of Observer II (p < 0.001). The highest interobserver correlation was found in the measurements in projection radiography in the AP method according to Dabbs and Fyllos. The measured values in men were 0.5 mm (SD 0.01 mm) larger than in women (p < 0.001), regardless of the method. The height of the intervertebral discs increases significantly until the age of 40, but beyond the age of 40, the height of the intervertebral discs either remains constant or falls off slightly, but not significantly. The lordosis angle of the lumbar spine and the concavity index of the vertebral bodies showed no correlation with the measured disc heights.

The radiological measurements to determine the intervertebral disc height have only moderate reliability. The results of X-rays are superior to those of MRI examination. The most accurate results are provided by measurements based on exact landmarks of the vertebral bodies. The method according to Dabbs seems to be the most accurate at the moment. There is no clear age-atypical chondrosis in patients without intervertebral disc damage.

Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However, the origin and development mechanism of the cheese-like morphology remain unclear. Here in this study, we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change. Transcriptome sequencing of the endplate chondrocytes under abnormal stress revealed that the Hippo signaling was key for this process. Activation of Hippo signaling or knockout of the key gene Yap1 in the cartilage endplate severed the cheese-like morphological change and disc degeneration after lumbar spine instability (LSI) surgery, while blocking the Hippo signaling reversed this process. Meanwhile, transcriptome sequencing data also showed osteoclast differentiation related gene set expression was up regulated in the endplate chondrocytes under abnormal mechanical stress, which was activated after the Hippo signaling. Among the discovered osteoclast differentiation gene set, CCL3 was found to be largely released from the chondrocytes under abnormal stress, which functioned to recruit and promote osteoclasts formation for cartilage endplate remodeling. Over-expression of Yap1 inhibited CCL3 transcription by blocking its promoter, which then reversed the endplate from remodeling to the cheese-like morphology. Finally, LSI-induced cartilage endplate remodeling was successfully rescued by local injection of an AAV5 wrapped Yap1 over-expression plasmid at the site. These findings suggest that the Hippo signaling induced osteoclast gene set activation in the cartilage endplate is a potential new target for the management of instability induced low back pain and lumbar degeneration.

As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.

Intervertebral disc (IVD) degeneration is a frequent cause of low back pain and is the most common cause of disability. Treatments for symptomatic IVD degeneration, including conservative treatments such as analgesics, physical therapy, anti-inflammatories and surgeries, are aimed at alleviating neurological symptoms. However, there are no effective treatments to prevent or delay IVD degeneration. Previous studies have identified risk factors for IVD degeneration such as aging, inflammation, genetic factors, mechanical overload, nutrient deprivation and smoking, but metabolic dysfunction has not been highlighted. IVDs are the largest avascular structures in the human body and determine the hypoxic and glycolytic features of nucleus pulposus (NP) cells. Accumulating evidence has demonstrated that intracellular metabolic dysfunction is associated with IVD degeneration, but a comprehensive review is lacking. Here, by reviewing the physiological features of IVDs, pathological processes and metabolic changes associated with IVD degeneration and the functions of metabolic genes in IVDs, we highlight that glycolytic pathway and intact mitochondrial function are essential for IVD homeostasis. In degenerated NPs, glycolysis and mitochondrial function are downregulated. Boosting glycolysis such as HIF1α overexpression protects against IVD degeneration. Moreover, the correlations between metabolic diseases such as diabetes, obesity and IVD degeneration and their underlying molecular mechanisms are discussed. Hyperglycemia in diabetic diseases leads to cell senescence, the senescence-associated phenotype (SASP), apoptosis and catabolism of extracellualr matrix in IVDs. Correcting the global metabolic disorders such as insulin or GLP-1 receptor agonist administration is beneficial for diabetes associated IVD degeneration. Overall, we summarized the recent progress of investigations on metabolic contributions to IVD degeneration and provide a new perspective that correcting metabolic dysfunction may be beneficial for treating IVD degeneration.

Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.

This study aimed to investigate the causal relationship between bone mineral density (BMD) and intervertebral disk degeneration (IVDD) using a two-sample bidirectional Mendelian randomization analysis. Summary-level data from the Genome-Wide Association Study (GWAS) were used. Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls). Bone mineral density (BMD) at five different sites (heel (n = 426,824), total body (TB) (n = 56,284), forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), and lumbar spine (LS) (n = 28,498)) was used as a phenotype for OP. Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods. Related sensitivity analyses were performed. Myopia was also analyzed as a negative control result to ensure the validity of IVs. Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta = 0.06, p = 0.03; TB-BMD-related analysis: beta = 0.18, p = 8.72E-08; FN-BMD-related analysis: beta = 0.15, p = 4.89E-03; LS-BMD-related analysis: beta = 0.16, p = 1.43E-04]. There was no evidence of a significant causal effect of IVDD on BMD. In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

Intervertebral disc degeneration is the primary etiology of low back pain and radicular pain. This review examines the roles of crucial chemokines in different stages of degenerative disc disease, along with interventions targeting chemokine function to mitigate disc degeneration.

The release of chemokines from degenerated discs facilitates the infiltration and activation of immune cells, thereby intensifying the inflammatory cascade response. The migration of immune cells into the venous lumen is concomitant with the emergence of microvascular tissue and nerve fibers. Furthermore, the presence of neurogenic factors secreted by disc cells and immune cells stimulates the activation of pain-related cation channels in the dorsal root ganglion, potentially exacerbating discogenic and neurogenic pain and intensifying the degenerative cascade response mediated by chemokines. Gaining a deeper comprehension of the functions of chemokines and immune cells in these processes involving catabolism, angiogenesis, and injury detection could offer novel therapeutic avenues for managing symptomatic disc disease.

Using whole spine sagittal T2 MRI, we aimed to compare the severity and prevalence of disc degeneration (DD) in axial SpA patients vs the general population and to determine any association between spinal inflammation, structural changes, mobility and DD among SpA patients.

Two prospectively collected cohorts of SpA patients (n = 411) and the general population (n = 2007) were recruited. Eventually, 967 participants from the populational cohort and 304 participants from the SpA cohort were analysed. Two hundred and nineteen matched pairs were generated by propensity score matching. Imaging parameters, including Pfirrmann grading, disc herniation, high-intensity zone, Schmorl's node, Modic change and anterior marrow change were studied and compared from C2/3 to L5/S1. DD was defined as Pfirrmann grade 4 or 5. Demographic factors, including age, sex and BMI, were collected. Multivariable linear regression was used to determine the association between spinal inflammation [Spondyloarthritis Research Consortium of Canada (SPARCC) spine MRI index], structural changes [modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)] and mobility (BASMI) with lumbar Pfirrmann score.

SpA patients had lower prevalence of DD (P < 0.001). The disease stage-stratified regression model showed that SPARCC spinal MRI index was associated with higher lumbar Pfirrmann scores in early disease (β = 0.196, P = 0.044), whereas mSASSS was associated with lower lumbar Pfirrmann scores in later disease (β = -0.138, P = 0.038). Males had higher mSASSS (P < 0.001) and lower odds of whole spine DD (odds ratio = 0.622, P = 0.028).

SpA patients had lower DD severity than the general population. Males had higher mSASSSs, and increased mSASSS at later disease was associated with less severe DD.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Some studies suggest sedentary behavior is a risk factor for musculoskeletal disorders. This study aimed to investigate the potential causal association between leisure sedentary behavior (LSB) (including television (TV) viewing, computer use, and driving) and the incidence of sciatica, intervertebral disk degeneration (IVDD), low back pain (LBP), and cervical spondylosis (CS).

We obtained the data of LSB, CS, IVDD, LBP, sciatica and proposed mediators from the gene-wide association studies (GWAS). The causal effects were examined by Inverse Variance Weighted (IVW) test, MR-Egger, weighted median, weighted mode and simple mode. And sensitivity analysis was performed using MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and MR-Egger intercept test. Multivariable MR (MVMR) was conducted to investigate the independent factor of other LSB; while two-step MR analysis was used to explore the potential mediators including Body mass index (BMI), smoking initiation, type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), schizophrenia, bipolar disorder between the causal association of LSB and these diseases based on previous studies.

Genetically associated TV viewing was positively associated with the risk of CS (OR = 1.61, 95%CI = 1.25 to 2.07, p = 0.002), IVDD (OR = 2.10, 95%CI = 1.77 to 2.48, p = 3.79 × 10-18), LBP (OR = 1.84, 95%CI = 1.53 to 2.21, p = 1.04 × 10-10) and sciatica (OR = 1.82, 95% CI = 1.45 to 2.27, p = 1.42 × 10-7). While computer use was associated with a reduced risk of IVDD (OR = 0.66, 95%CI = 0.55 to 0.79, p = 8.06 × 10-6), LBP (OR = 0.49, 95%CI = 0.40 to 0.59, p = 2.68 × 10-13) and sciatica (OR = 0.58, 95%CI = 0.46 to 0.75, p = 1.98 × 10-5). Sensitivity analysis validated the robustness of MR outcomes. MVMR analysis showed that the causal effect of TV viewing on IVDD (OR = 1.59, 95%CI = 1.13 to 2.25, p = 0.008), LBP (OR = 2.15, 95%CI = 1.50 to 3.08, p = 3.38 × 10-5), and sciatica (OR = 1.61, 95%CI = 1.03 to 2.52, p = 0.037) was independent of other LSB. Furthermore, two-step MR analysis indicated that BMI, smoking initiation, T2DM may mediate the causal effect of TV viewing on these diseases.

This study provides empirical evidence supporting a positive causal association between TV viewing and sciatica, IVDD and LBP, which were potentially mediated by BMI, smoking initiation and T2DM.

Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.

Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse sequalae such as fractures and even death. The incidence and prevalence of degenerative musculoskeletal disorders is rising owing to the aging of the world's population. The Notch signaling pathway, which is expressed in almost all organ systems, extensively regulates cell proliferation and differentiation as well as cellular fate. Notch signaling shows increased activity in degenerative musculoskeletal disorders and retards the progression of degeneration to some extent. The review focuses on four major degenerative musculoskeletal disorders (osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia) and summarizes the pathophysiological functions of Notch signaling in these disorders, especially its role in stem/progenitor cells in each disorder. Finally, a conclusion will be presented to explore the research and application of the perspectives on Notch signaling in degenerative musculoskeletal disorders.

To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP.

We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery. Relevant occupational and demographic data from all patients were statistically analyzed, and all variables were made categorical. Forward stepwise logistic regression models were constructed for preoperative chronic neck pain to explore the possible risk factors associated with chronic neck pain.

The differences in smoking, being an office worker, BMI, and disease types between NP and no-NP groups were statistically significant. In contrast, there were no statistically significant in age, sex, academic level, duration, and degeneration grade between the two groups. Moreover, further logistic regression analysis indicated that smoking, being an office worker, having an abnormal BMI, and cervical spondylotic radiculopathy (CSR) were related to chronic neck pain.

The present study indicated that smoking, being an office worker, having an abnormal BMI, and CSR were predisposing risk factors for NP associated with cervical degenerative disease. Although intervertebral disc degeneration is the pathology basis of NP, the degeneration grade was not related to the occurrence of NP in our current study. Therefore, quitting smoking, avoiding sedentariness, and maintaining a normal BMI may prevent NP to some extent.

Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.

Introduction Hypercholesterolemia is known to be a major contributor to the morbidity associated with cardiovascular disease and has been hypothesized to result in degenerative changes to the spine through atherosclerosis of segmental lumbar vessels. The purpose of this study is to determine the relationship between hypercholesterolemia and degenerative lumbar spine conditions in a U.S. cohort. Methods A total of 30,461 participated in the 2018 Medicare Expenditure Panel Survey (MEPS). Of those, 1,063 subjects responded to whether a diagnosis of lumbar disorders with low back pain was present. Odds ratios (OR) were calculated, and logistic regression analyses were adjusted for demographic, education, occupation, cardiovascular and mental health conditions. Results Of the 1,063 respondents, 455 (43%) reported back pain. Mean age of the respondents was 62.7±16.1. Men and women reported back pain at similar rates (43% vs 45%, p=0.664). Age, race, education level and occupation were similar between those with and without back pain (p>0.05). Those with a diagnosis of depression had higher odds of having back pain (p<0.05). Prevalence of back pain in subjects who responded to the back pain diagnosis item on the survey was 42.6%. On univariate analysis, diagnosis of total cholesterol levels was significantly higher in those with a diagnosis of back pain (OR 1.36, 95% CI [1.20-1.54], p<.0001). Multivariable analysis showed that hypercholesterolemia was independently associated with back pain (adjusted OR 1.32, 95% CI [1.04-1.68], p=0.021) after controlling for covariates. Conclusions In this study, subjects with hypercholesterolemia were 34% more likely to have back pain after controlling for confounders which presents as a recent discovery amongst U.S. populations. Further studies should be performed to investigate the management of hypercholesterolemia in the development and progression of degenerative lumbar back pain.

An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).

Cardiovascular risk factors (hypertension, dyslipidemia, and type II diabetes) have been proposed as risk factors for back pain. However, few longitudinal studies have found significant associations between cardiovascular risk factors and back pain, and these may be explained by confounding or reverse causation.

To examine potential causal effects of cardiovascular risk factors on back pain, and vice versa.

Bidirectional Mendelian randomization (MR) study.

Genome-wide association studies (GWAS) with sample sizes between 173,082 and 1,028,947 participants.

Outcomes included (1) back pain associated with health care use (BP-HC) in the forward MR; and (2) seven cardiovascular phenotypes in the reverse MR, including 2 measurements used for the evaluation of hypertension (diastolic blood pressure and systolic blood pressure), 4 phenotypes related to dyslipidemia (LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides), and type II diabetes.

We used summary statistics from large, publicly available GWAS for BP-HC and the 7 cardiovascular phenotypes to obtain genetic instrumental variables. We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis, Causal Analysis Using Summary Effect (CAUSE), and sensitivity analyses.

In forward MR analyses of seven cardiovascular phenotypes, diastolic blood pressure was associated with BP-HC across all analyses (IVW estimate: OR = 1.10 per 10.5 mm Hg increase [1.04-1.17], p-value = .001), and significant associations of systolic blood pressure with BP-HC were also found (IVW estimate: OR = 1.09 per 19.3 mm Hg increase [1.04-1.15], p-value = .0006). In reverse MR analyses, only type II diabetes was associated with BP-HC across all analyses (IVW estimate: OR = 1.40 [1.13-1.73], p-value = .002).

These findings from analyses of large, population-based samples indicate that higher blood pressure increases the risk of BP-HC, and BP-HC itself increases the risk of type II diabetes.

There is an enormous body of literature that has identified the intervertebral disc as a potent pain generator. However, with regard to lumbar degenerative disc disease, the specific diagnostic criteria lack clarity and fail to capture the primary components which include axial midline low back pain with or without non-radicular/non-sciatic referred leg pain in a sclerotomal distribution. In fact, there is no specific ICD-10-CM diagnostic code to classify and define discogenic pain as a unique source of pain distinct from other recognized sources of chronic low back pain including facetogenic, neurocompressive including herniation and/or stenosis, sacroiliac, vertebrogenic, and psychogenic. All of these other sources have well-defined ICD-10-CM codes. Corresponding codes for discogenic pain remain absent from the diagnostic coding vernacular. The International Society for the Advancement of Spine Surgery (ISASS) has proposed a modernization of ICD-10-CM codes to specifically define pain associated with lumbar and lumbosacral degenerative disc disease. The proposed codes would also allow the pain to be characterized by location: lumbar region only, leg only, or both. Successful implementation of these codes would benefit both physicians and payers in distinguishing, tracking, and improving algorithms and treatments for discogenic pain associated with intervertebral disc degeneration.

Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.

Quantitative analysis of the trace element content of human intervertebral discs (IVDs) is essential because it can identify specific enzymes or metabolites that may be related to human intervertebral disc degeneration (IVDD). The goal of this study was to assess the concentrations of copper (Cu), iron (Fe), manganese (Mn), lead (Pb), zinc (Zn), sodium (Na), magnesium (Mg), potassium (K), phosphorus (P), and calcium (Ca) in serum samples obtained from patients with IVDD in comparison to healthy volunteers (a control group). The study group consisted of 113 Caucasian patients qualified by a specialist neurosurgeon for microdiscectomy. The control group consisted of 113 healthy volunteers who met the eligibility criteria for blood donors. The examined clinical material was the serum samples obtained from both groups.Based on the quantitative analysis of selected elements, there were statistically significantly (p 0.05) higher concentrations of Cu (1180 μg/L±800 μg/L vs. 1230 μg/L±750 μg/L), Zn (790 μg/L±300 μg/L vs. 850 μg/L±200 μg/L), and Mg (21730 μg/L±4360 μg/L vs. 23820 μg/L±4990 μg/L) in the serum of healthy volunteers compared to those in the study group. In addition, statistically significant changes were not detected in the concentrations of any elements among either sex in either the study or control group or in their body mass index (BMI) values (p > 0.05). In the serum samples from the study group, the strongest relationships were noted between the concentrations of Zn and Pb (r = 0.61), Zn and P (r = 0.69), Zn and Ca (r = 0.84), Zn and Cu (r = 0.83), Mg and Ca (r = 0.74), and Ca and P (r = 0.98).It has been indicated that, above all, the concentrations of Cu, Zn, Ca, and Mg depend on the advancement of radiological changes, according to the Pfirrmann scale. However, no influence on pain intensity was found, depending on the concentration of the assessed elements.The analysis indicates that the determination of serum Cu, Zn, Ca, and Mg concentrations may have diagnostic significance in predicting the onset of lumbosacral IVDD. The predictive evaluation of changes in the concentrations of selected elements in patients with degenerative lumbar IVD lesions appears to be a promising, cost-effective strategy.

The present work had as its main objective the development of a method for localizing and automatically segmenting lumbar intervertebral discs (IVD) in 3D from magnetic resonance imaging (MRI), with the goal of supporting the generation of finite element (FE) models from actual lumbar spine anatomy, by providing accurate and personalized information on the shape of the patient's IVD. The extension of the method to allow performing separate segmentations of the IVD's two main structures - annulus fibrosus (AF) and nucleus pulposus (NP) - as well as automatically detecting degenerated IVD where this distinction is no longer possible was also an objective of the work.

The method presented here evolves from 2D segmentations in the sagittal profile using Gabor filters towards 3D segmentations. It works by detecting the spine curves and intensity regions corresponding to IVD. As so, the 2D method from Zhu et al. (2013) was partially implemented, modified and adapted to 3D use, and then tested with eight spines from two separated online datasets. The 3D adaptation was achieved by using vertebral body segmentation masks to approximate the shape of the vertebrae and to adjust the spine curves accordingly.

The method showed average values of 85%, 83% and 96% for the Dice coefficient, sensitivity and specificity, respectively. The method correctly identified 65 of 68 (96%) IVD as either healthy or degenerated. The method's Dice coefficient is within the range of existing 3D IVD segmentation methods in the literature (81-92%). The method took on average 6-7 s to perform a full 3D segmentation, which is well within the range of the existing methods (2 s - 19 min).

The developed method can be used to generate accurate 3D models of the IVD based on MRI, with AF/NP distinction and detection of marked degeneration by comparing each IVD with the remaining spine levels. Further work shall improve the method towards distinguishing between specific levels of degeneration for clinically oriented FE modeling.

Stem cell therapy has been increasingly investigated as a promising strategy for intervertebral disc degeneration (IDD). However, no international analysis of stem cell research has yet been conducted. This study aimed to analyze the major characteristics of published reports of stem cell use for IDD and to present a global insight into stem cell research. The study period spanned from the inception of the Web of Science database to 2021. A search strategy using specific keywords was implemented to retrieve relevant publications. The numbers of documents, citations, countries, journals, article types, and stem cell types were evaluated. A total of 1170 papers were retrieved. The analysis showed a significant increase in the number of papers over time (p < 0.001). High-income economies accounted for the majority of papers (758, 64.79 %). China produced the most articles (378, 32.31 %), followed by the United States (259, 22.14 %), Switzerland (69, 5.90 %), United Kingdom (54, 4.62 %), and Japan (47, 4.02 %). The United States ranked first in terms of the number of citations (10,346), followed by China (9177) and Japan (3522). Japan ranked first in terms of the number of citations per paper (74.94), followed by United Kingdom (58.54) and Canada (53.74). When standardized by population, Switzerland ranked first, followed by Ireland and Sweden. When gross domestic product was considered, Switzerland ranked first, followed by Portugal and Ireland. The number of papers was positively correlated with gross domestic product (p < 0.001, r = 0.673); however, there was no significant correlation with population (p = 0.062, r = 0.294). Mesenchymal stem cells were the most investigated stem cells, followed by nucleus pulposus-derived stem cells and adipose-derived stem cells. A sharp increase in stem cell research was observed in the field of IDD. China produced the most, although several European countries were more productive relative to their populations and economies.

The degenerative disease of the intervertebral disc is nowadays an important health problem, which has still not been understood and solved adequately. The vertebral endplate is regarded as one of the vital elements in the structure of the intervertebral disc. Its constituent cells, the chondrocytes in the endplate, may also be involved in the process of the intervertebral disc degeneration and their role is central both under physiological and pathological conditions. They main functions include a role in homeostasis of the extracellular environment of the intervertebral disc, metabolic support and nutrition of the discal nucleus and annulus beneath and the preservation of the extracellular matrix. Therefore, it is understandable that the cells in the endplate have been in the centre of research from several viewpoints, such as development, degeneration and growth, reparation and remodelling, as well as treatment strategies. In this article, we briefly review the importance of vertebral endplate, which are often overlooked, in the intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) demonstrates a gradually increased incidence and has developed into a major health problem worldwide. The nucleus pulposus is characterized by the hypoxic and avascular environment, in which hypoxia-inducible factor-1α (HIF-1α) has an important role through its participation in extracellular matrix synthesis, energy metabolism, cellular adaptation to stresses and genesis. In this study, the effects of HIF-1α on mouse primary nucleus pulposus cells (MNPCs) exposed to TNF-α were observed, the potential mechanism was explored and a rabbit IVDD model was established to verify the protective role of HIF-1α on IVDD. In vitro results demonstrated that HIF-1α could attenuate the inflammation, apoptosis and mitochondrial dysfunction induced by TNF-α in MNPCs; promote cellular anabolism; and inhibit cellular catabolism. In vivo results demonstrated that after establishment of IVDD model in rabbit, disc height and IVD extracellular matrix were decreased in a time-dependent manner, MRI analysis showed a tendency for decreased T2 values in a time-dependent manner and supplementation of HIF-1α improved histological and imaginative IVDD while downregulation of HIF-1α exacerbated this degeneration. In summary, HIF-1α protected against IVDD, possibly through reducing ROS production in the mitochondria and consequent inhibition of inflammation, metabolism disorders and apoptosis of MNPCs, which provided a potential therapeutic instrument for the treatment of IVDD diseases.

The completeness of the intervertebral disc proteome is fundamental to the integrity and functionality of the intervertebral disc.

The 20 experimental rats were placed into two groups randomly, normal group (NG) and acupuncture pathological degeneration group-2 weeks (APDG-2w). The ten 24-month-old rats were grouped into physiological degeneration group (PDG). Magnetic resonance imaging, X-ray examination, histological staining (hematoxylin & eosin, safranin-O cartilage, and alcian blue staining), and immunohistochemical examination were carried out for assessing the degree of disc degradation. Intervertebral disc was collected, and protein composition was determined by LC- MS, followed by bioinformatic analysis including significance analysis, subcellular localization prediction, protein domain prediction, GO function and KEGG pathway analysis, and protein interaction network construction. LC-PRM was done for protein quantification.

Physiological degeneration and especially needle puncture decreased T2 signal intensity and intervertebral disc height. Results from hematoxylin & eosin, safranin-O, and alcian blue staining revealed that the annulus fibrosus apparently showed the wavy and collapsed fibrocartilage lamellas in APDG-2w and PDG groups. The contents of the nucleus pulposus were decreased in physiological degeneration group and APDG-2w group compared with NG. Results from immunohistochemical analysis suggested the degeneration of intervertebral disc and inflammation in APDG-2w and PDG groups. The protein composition and expression between needle puncture rat models and the physiological degeneration group showed significant difference.

Our studies produced point-reference datasets of normal rats, physiological degeneration rats, and needle puncture rat models, which is beneficial to subsequent pathological studies. There is differential expression of protein expression in degenerative discs with aging and acupuncture, which may be used as a potential discriminating index for different intervertebral degenerations.

Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of LEP single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the LEP SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals (p < 0.001) and non-obese or obese women (p < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals (p = 0.011, p = 0.012). Further, the association between these LEP SNPs and leptin levels was significant only in obese women (p = 0.025 and p = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction p = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the LEP transcription effect.

Degenerative changes in the lumbar spine significantly reduce the quality of life of people. In order to fully understand the biomechanics of the affected spine, it is crucial to consider the biomechanical alterations caused by degeneration of the intervertebral disc (IVD). Therefore, this study is aimed at the development of a discrete element model of the mechanical behavior of the L4-L5 spinal motion segment, which covers all the degeneration grades from healthy IVD to its severe degeneration, and numerical study of the influence of the IVD degeneration on stress state and biomechanics of the spine. In order to analyze the effects of IVD degeneration on spine biomechanics, we simulated physiological loading conditions using compressive forces. The results of modeling showed that at the initial stages of degenerative changes, an increase in the amplitude and area of maximum compressive stresses in the disc is observed. At the late stages of disc degradation, a decrease in the value of intradiscal pressure and a shift in the maximum compressive stresses in the dorsal direction is observed. Such an influence of the degradation of the geometric and mechanical parameters of the tissues of the disc leads to the effect of bulging, which in turn leads to the formation of an intervertebral hernia.

The purpose of this study was to investigate in cadaveric specimens the reliability of measuring cervical intradiscal pressure (CIDP) and if posterior-anterior (PA) mobilizations targeting the cervical spine were associated with CIDP changes.

Cervical PA mobilizations were performed on the spinous processes of 7 (3 men, 4 women) cadaveric specimens using a servo-controlled linear actuator to provide 25N and 45N forces. CIDP measurements were performed at C4-5, C5-6, C6-7, and C7-T1 intervertebral discs (IVDs) using a fiberoptic catheter system that recorded CIDP for each IVD cervical segment. To assess CIDP measurement reliability, the intraclass correlation coefficient (ICC [3,k]) was calculated. Repeated measures Friedman analysis of variance assessed effect of cervical mobilizations on CIDP for before, during, and immediately after mobilization at 25N and 45N forces for each cervical IVD segment.

All CIDP measurements demonstrated excellent reliability (ICC >0.98). During the 25N mobilizations, the median CIDP varied from -0.12 to 0.91 (interquartile range, 5.22-5.36), while for 45N mobilizations the median ranged from -0.94 to 1.21 (interquartile range, -7.74 to 43.49). These changes were not statistically significant (P > .40) during 25N and 45N PA mobilizations, with the exception of C5-6 CIDP at 25N and 45N (P = .05 and .018, respectively).

There was high CIDP variability between cadavers during and after mobilization. Mobilizations of 1 cervical vertebra resulted in both CIDP increase or decrease at adjacent and remote cervical IVD segments that were not consistent. Cervical PA mobilizations produced variable CIDP changes at adjacent and remote cervical segments in cadavers.