The influence of proliferative tissue on Hounsfield unit and its correlation with BMD in middle-aged and elderly patients with lumbar degenerative diseases.

PURPOSE: The difference of Hounsfield Unit (HU) value in different regions of L3 vertebra in middle-aged and elderly patients with lumbar degeneration diseases (LDD) was analyzed. To investigate the influence of proliferative tissue on HU value of cancellous bone and its correlation with bone mineral density (BMD). METHODS: The medical records of middle-aged and elderly patients with LDD in our hospital from December 2020 to December 2023 were retrospectively analyzed. The patients were divided into osteophyte group and no-osteophyte group according to the presence or absence of osteophyte formation on lumbar spine X-ray. In osteophyte group, cancellous bone HU value, containing cortical bone overall HU value and containing osteophyte overall HU value in L3 vertebra were measured on the lumbar CT cross-section. In no-osteophyte group, only the cancellous bone HU value and the containing cortical bone overall HU value were measured. Differences in HU value in different regions of the L3 vertebral body were compared within and between groups of middle-aged and elderly patients with LDD, respectively. To investigate its effect on cancellous bone HU measurements and to do a correlation analysis with patients' BMD. RESULTS: A total of 115 patients with LDD were included in this study, including 65 males and 50 females, with an average age of 67.83 ± 6.59 years. The results of the study showed no statistical differences in age (P = 0.15), gender (P = 0.57), smoking (P = 0.88), drinking history (P = 0.76), medical history (P > 0.05) and BMI(P = 0.29) between the two groups. In osteophyte group, the mean cancellous bone HU value was 98.00 ± 25.50 HU, the containing cortical bone overall HU value was 189.02 ± 46.18 HU, and the containing osteophyte overall HU value was 232.69 ± 56.01 HU. The overall HU values containing cortical bone and containing osteophyte were significantly higher than cancellous bone HU value (P < 0.001). In no-osteophyte group, the mean cancellous bone HU value was 102.04 ± 19.64 HU, and the containing cortical bone overall HU value was 175.00 ± 28.97 HU, which was statistically significantly different (P < 0.001). There was no significant difference in cancellous bone HU value and the containing cortical bone overall HU value between the two groups (P > 0.05). The results of the Pearson correlation analysis showed a significant correlation between the cancellous bone HU value of the L3 vertebrae and the QCT BMD value of the patients (r = 0.95, P < 0.001). However, there was no significant correlation between containing cortical bone overall HU value and containing osteophyte overall HU value and the patient's QCT BMD value (P > 0.05). CONCLUSIONS: Vertebral HU value is an alternative measurement that effectively reflects the patient's BMD. In middle-aged and elderly LDD patients, HU values in different areas of L3 vertebra are significantly different, and hyperplastic tissues such as cortical bone and osteophytes may exponentially lead to higher HU value in patients. Compared with other measurement areas, vertebral cancellous bone HU value have the advantage of accurately assessing patients' BMD.

Gait assessment in a female rat Sprague Dawley model of disc-associated low back pain.

PURPOSE: Gait disturbances are common in human low back pain (LBP) patients, suggesting potential applicability to rodent LBP models. This study aims to assess the influence of disc-associated LBP on gait in female Sprague Dawley rats and explore the utility of the open-source Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) suite as a potential alternative tool for spontaneous pain assessment in a previously established LBP model. MATERIALS AND METHODS: Disc degeneration was surgically induced using a one-level disc scrape injury method, and microcomputed tomography was used to assess disc volume loss. After disc injury, axial hypersensitivity was evaluated using the grip strength assay, and an open field test was used to detect spontaneous pain-like behavior. RESULTS: Results demonstrated that injured animals exhibit a significant loss in disc volume and reduced grip strength. Open field test did not detect significant differences in distance traveled between sham and injured animals. Concurrently, animals with injured discs did not display significant gait abnormalities in stance time imbalance, temporal symmetry, spatial symmetry, step width, stride length, and duty factor compared to sham. However, comparisons with reference values of normal gait reported in prior literature reveal that injured animals exhibit mild deviations in forelimb and hindlimb stance time imbalance, forelimb temporal symmetry, and hindlimb spatial symmetry at some time points. CONCLUSIONS: This study concludes that the disc injury may have very mild effects on gait in female rats within 9 weeks post-injury and recommends future in depth dynamic gait analysis and longer studies beyond 9 weeks to potentially detect gait.

[Endoplasmic reticulum quality control system: a potential target for the treatment of intervertebral disc degeneration].

As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays a crucial role in regulating intracellular protein folding, translation and assembly. Multiple quality control mechanisms in the ER ensure accurate modification of proteins in the ER lumen are accurately modified, thus maintaining calcium homeostasis, oxidative stress, cellular senescence and apoptosis. These mechanisms include ER stress (ERS), ER autophagy (ER-phagy, ERPA) and ER-associated degradation (ERAD). Intervertebral disc degeneration (IDD) is an age-related degenerative disease of the spine. Although the pathogenesis of IDD has not been fully elucidated, emerging evidence suggests that the ER quality control system may be involved in its progression. Previous studies have focused on mitochondrial quality control and its related mechanisms in diseases, with limited systematic summaries on the ER quality control system. In this paper, we comprehensively reviewed the molecular mechanisms of the ER quality control system and investigated its association with IDD. In addition, we summarized the potential therapeutic strategies targeting the ER quality control system to attenuate IDD progression, offering new insights into the pathogenesis and regenerative repair strategies of IDD.

Osteoporosis, spinal degenerative disorders, and their association with low back pain, activities of daily living, and physical performance in a general population.

Osteoporosis, vertebral fractures, and spinal degenerative diseases are common conditions that often coexist in older adults. This study aimed to determine the factors influencing low back pain and its impact on activities of daily living (ADL) and physical performance in older individuals with multiple comorbidities. This cross-sectional study was part of a large-scale population-based cohort study in Japan, involving 1009 participants who underwent spinal magnetic resonance imaging (MRI) to assess cervical cord compression, radiographic lumbar spinal stenosis, and lumbar disc degeneration. Vertebral fractures in the thoracolumbar spine were evaluated using sagittal MRI with a semi-quantitative method. Bone mineral density was measured using dual-energy X-ray absorptiometry. Low back pain, Oswestry Disability Index (ODI), and physical performance tests, such as one-leg standing time, five times chair-stand time, maximum walking speed, and maximum step length, were assessed. Using clinical conditions as objective variables and image evaluation parameters as explanatory variables, multiple regression analysis showed that vertebral fractures were significantly associated with low back pain and ODI. Vertebral fractures and osteoporosis significantly impacted physical performance, whereas osteoporosis alone did not affect low back pain or ODI. Our findings contribute to new insights into low back pain and its impact on ADL and physical performance.

Biomechanical analysis of single and multi-level artificial disc replacement (ADR) in cervical spine using multi-scale loadings: A finite element study.

Artificial disc replacement (ADR) is a clinical procedure used to diagnose cervical degenerative disc disease, preserving range of motion (ROM) at the fixation level and preventing adjacent segment degeneration (ASD). This study analyzed the biomechanics of ADR by examining range of motion (ROM), stress levels in bone and implants, and strain in the bone-implant interface using multi-scale loadings. The study focused on single- and double-level patients across various loading scales during physiological motions within the cervical spine. Results showed increased ROM in single-level and double-level fixations during physiological loadings, while ROM decreased at the adjacent level of fixation with the intact cervical spine model. The Prodisc-Implant metal endplate experienced a maximum von Mises stress of 432 MPa during axial rotation, confirming the long durability and biomechanical performance of the bone-implant interface.

Effect of device constraint: a comparative network meta-analysis of ACDF and cervical disc arthroplasty.

BACKGROUND CONTEXT: Clinical trials have demonstrated that cervical disc arthroplasty (CDA) is an effective and safe alternative treatment to anterior cervical discectomy and fusion (ACDF) for cervical degenerative disc disease in the appropriately indicated patient population. Various devices for CDA exist, differing in the level of device constraint. PURPOSE: To investigate outcomes following Anterior Cervical Discectomy and Fusion (ACDF) versus CDA stratified based on the level of device constraint: Constrained, Semiconstrained, and Unconstrained. STUDY DESIGN: Systematic review and network meta-analysis. PATIENT SAMPLE: A total of 2,932 CDA patients (979 Constrained, 1,214 Semiconstrained, 739 Unconstrained) and 2,601 ACDF patients from 41 studies that compared outcomes of patients undergoing CDA or ACDF at a single level at a minimum of 2 years follow-up. OUTCOME MEASURES: Outcomes of interest included the development of adjacent segment degeneration (ASD), index and adjacent segment reoperation rates, range of motion (ROM), high-grade heterotopic ossification (HO, McAfee Grades 3/4), and patient-reported outcomes (NDI/VAS). METHODS: CDA devices were grouped based on the degrees of freedom (DoF) allowed by the device, as either Constrained (3 DoF), Semiconstrained (4 or 5 DoF), or Unconstrained (6 DoF). A random effects network meta-analysis was conducted using standardized mean differences (SMD) and log relative risk (RR) were used to analyze continuous and categorical data, respectively. RESULTS: Semiconstrained (p=.03) and Unconstrained CDA (p=.01) demonstrated a significantly lower risk for ASD than ACDF. All levels of CDA constraint demonstrated a significantly lower risk for subsequent adjacent segment surgery than ACDF (p<.001). Semiconstrained CDA also demonstrated a significantly lower risk for index level reoperation than both ACDF and Constrained CDA (p<.001). Unconstrained devices retained significantly greater ROM than both Constrained and Semiconstrained CDA (p<.001). As expected, all levels of device constraint retained significantly greater ROM than ACDF (p<.001). Constrained and Unconstrained devices both demonstrated significantly lower levels of disability on NDI than ACDF (p=.02). All levels of device constraint demonstrated significantly less neck pain than ACDF (p<.05), while Unconstrained CDA had significantly less arm pain than ACDF (p=.02) at final follow-up greater than 2 years. CONCLUSION: CDA, particularly the unconstrained and semiconstrained designs, appears to be more effective than ACDF in reducing the risk of adjacent segment degeneration and the need for further surgeries, while also allowing for greater range of motion and better patient-reported outcomes. Less constrained CDA conferred a lower risk for index level reoperation, while also retaining more range of motion than more constrained devices.

Biomechanics of annulus fibrosus: Elastic fiber simplification and degenerative impact on damage initiation and propagation.

This study addresses three primary objectives related to lumbar intervertebral disc (IVD) biomechanics under ramping quasi-static loading conditions. First, we explore the conditions justifying the simplification of axisymmetric elastic fiber families into single fiber bundles through discretized strain energy functions. Simulations reveal that a concentration factor exceeding 10 allows for a consistent deviation below 10% between simplified and non-simplified responses. Second, we investigate the impact of elastic fibers on the physiological stiffness in IVDs, revealing minimal influence on biological motions but significant effects on degeneration. Lastly, we examine the initiation and progression of annulus fibrosus (AF) damage. Our findings confirm the validity of simplifying elastic fiber families and underscore the necessity of considering elastic fiber damage in biomechanical studies of AF tissues. Elastic fibers contribute to increased biaxial stretch stiffness, and their damage significantly affects the loading capacity of the inner AF. Additionally, degeneration significantly alters the susceptibility to damage in the AF, with specific regions exhibiting higher vulnerability. Damage tends to extend circumferentially and radially, emphasizing the regional variations in collagen and elastic fiber properties. This study offers useful insights for refining biomechanical models, paving the way for a more comprehensive understanding of IVD responses and potential clinical implications.

Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family.

Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.

Is the disappearance of the cervical flexion-relaxation phenomenon associated with cervical degeneration in healthy people?

PURPOSE: This study aims to explore the differences in cervical degeneration between healthy people with and without cervical flexion-relaxation phenomenon (FRP) and to identify whether the disappearance of cervical FRP is related to cervical degeneration. METHODS: According to the flexion relaxation ratio (FRR), healthy subjects were divided into the normal FRP group and the abnormal FRP group. Besides, MRI was used to evaluate the degeneration of the passive subsystem (vertebral body, intervertebral disc, cervical sagittal balance, etc.) and the active subsystem (deep flexors [DEs], deep extensors [DFs], and superficial extensors [SEs]). In addition, the correlation of the FRR with the cervical degeneration score, C2-7Cobb, Borden method, relative total cross-sectional area (rTCSA), relative functional cross-sectional area (rFCSA), and fatty infiltration ratio (FIR) was analyzed. RESULTS: A total of 128 healthy subjects were divided into the normal FRP group (n=52, 40.63%) and the abnormal FRP group (n=76, 59.38%). There were significant differences between the normal FRP group and the abnormal FRP group in the cervical degeneration score (z=-6.819, P<0.001), C2-7Cobb (t=2.994, P=0.004), Borden method (t=2.811, P=0.006), and FIR of DEs (t=-4.322, P<0.001). The FRR was significantly correlated with the cervical degeneration score (r=-0.457, P<0.001), C2-7Cobb (r=0.228, P=0.010), Borden method (r=0.197, P=0.026), and FIR of DEs (r=-0.253, P=0.004). CONCLUSION: The disappearance of cervical FRP is related to cervical degeneration. A new hypothesis mechanism for FRP is proposed. The cervical FRP test is an effective and noninvasive examination for the differential diagnosis of healthy people, people with potential NSNP, and patients with NSNP.

Enzymatic denaturation versus excessive fatigue loading degeneration: Effects on the time-dependent response of the intervertebral disc.

Degenerative disc disease (DDD), regardless of its phenotype and clinical grade, is widely associated with low back pain (LBP), which remains the single leading cause of disability worldwide. This work provides a quantitative methodology for comparatively investigating artificial IVD degeneration via two popular approaches: enzymatic denaturation and fatigue loading. An in-vitro animal study was used to study the time-dependent responses of forty fresh juvenile porcine thoracic IVDs in conjunction with inverse and forward finite element (FE) simulations. The IVDs were dissected from 6-month-old-juvenile pigs and equally assigned to 5 groups (intact, denatured, low-level, medium-level, high-level fatigue loading). Upon preloading, a sinusoid cyclic load (Peak-to-peak/0.1-to-0.8 MPa) was applied (0.01-10 Hz), and dynamic-mechanical-analyses (DMA) was performed. The DMA outcomes were integrated with a robust meta-model analysis to quantify the poroelastic IVD characteristics, while specimen-specific FE models were developed to study the detailed responses. The results demonstrated that enzymatic denaturation had a more significantly pronounced effect on the resistive strength and shock attenuation capabilities of the intervertebral discs. This can be attributed to the simultaneous disruption of the collagen fibers and water-proteoglycan bonds induced by trypsin digestion. Fatigue loading, on the other hand, primarily influenced the disc's resistance to deformation in a frequency-dependent pattern, where alterations were most noticeable at low loading frequencies. This study confirms the intricate interplay between the biochemical changes induced by enzymatic processes and the mechanical behavior stemming from fatigue loading, suggesting the need for a comprehensive approach to closely mimic the interrelated multifaceted processes of human disc degeneration.

Biomechanical Comparison of Different Surgical Strategies for Skip-level Cervical Degenerative Disc Disease: A Finite Element Study.

STUDY DESIGN: We constructed finite element (FE) models of the cervical spine consisting of C2-C7 and predicted the biomechanical effects of different surgical procedures and instruments on adjacent segments, internal fixation systems, and the overall cervical spine through FE analysis. OBJECTIVE: To compare the biomechanical effects between the zero-profile device and cage-plate device in skip-level multistage anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is often considered the standard treatment for degenerative cervical spondylosis. However, the selection of surgical methods and instruments in cases of skip-level cervical degenerative disk disease is still controversial. MATERIALS AND METHODS: Three FE models were constructed, which used noncontiguous 2-level Zero-P (NCZP) devices for C3/4 and C5/6, a noncontiguous 2-level cage-plate (NCCP) for C3/4 and C5/6, and a contiguous 3-level cage-plate (CCP) for C3/6. Simulate daily activities in ABAQUS. The range of motion (ROM), von Mises stress distribution of the endplate and internal fixation system, and intervertebral disk pressure (IDP) of each model were recorded and compared. RESULTS: Similar to the stress of the cortical bone, the maximum stress of the Zero-P device was higher than that of the CP device for most activities. The ROM increments of the superior, inferior, and intermediate segments of the NCZP model were lower than those of the NCCP and CCP models in many actions. In terms of the IDP, the increment value of stress for the NCZP model was the smallest, whereas those of the NCCP and CCP models were larger. Similarly, the increment value of stress on the endplate also shows the minimum in the NCZP model. CONCLUSIONS: Noncontiguous ACDF with zero profile can reduce the stress on adjacent intervertebral disks and endplates, resulting in a reduced risk of adjacent segment disease development. However, the high cortical bone stress caused by the Zero-P device may influence the risk of fractures.

Biomechanical repercussion of sitting posture on lumbar intervertebral discs: A systematic review.

BACKGROUND: The static sitting position contributes to increased pressure on the lumbar intervertebral disc, which can lead to dehydration and decreased disc height. OBJECTIVE: To systematically investigate the of sitting posture on degeneration of the lumbar intervertebral disc. MATERIALS AND METHODS: One researcher carried out a systematic literature search of articles with no language or time limits. Studies from 2006 to 2018 were found. The searches in all databases were carried out on January 28, 2022, using the following databases: Pubmed, Scopus, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro) databases, and for the grey literature: Google scholar, CAPES Thesis and Dissertation Bank, and Open Grey. The acronym PECOS was used to formulate the question focus of this study: P (population) - male and female subjects; E (exposure) - sitting posture; C (comparison) - other posture or sitting posture in different periods; O (outcomes) - height and degeneration of the lumbar intervertebral disc(s), imaging exam; and S (study) - cross-sectional and case control. RESULTS: The risk of bias was in its moderate totality in its outcome: height and degeneration of the lumbar intervertebral disc(s) - imaging. Of the four selected studies, three found a decrease in the height of the disc(s) in sitting posture. CONCLUSION: The individual data from the manuscripts suggest that the sitting posture causes a reduction in the height of the lumbar intervertebral disc. It was also concluded that there is a need for new primary studies with a more in-depth design and sample size.

Biomechanical investigation of a customized interspinous spacer system in the treatment of degenerative disc diseases: A finite element analysis.

BACKGROUND: A novel interspinous fixation system based on anatomical parameters and incorporating transfacetopedicular screws, was developed to treat degenerative disc diseases. The biomechanical characteristics of the novel system were evaluated using finite element analysis in comparison to other classical interspinous spacers. METHODS: The L1-S1 lumbar spine finite element models were surgically implanted with the novel system, Coflex and DIAM devices at the L4/L5 segment to assess the range of motion, the pression distribution of intervertebral disc, the peak stresses on the spinous process and implant during various motions. FINDINGS: Range of motions of the L4/L5 surgical segment were reduced by 29.13%, 61.27%, 77.35%, 33.33%, and the peak stresses of intervertebral disc were decreased by 36.82%, 67.31%, 73.00%, 69.57% for the novel system in flexion, extension, lateral bending, and axial rotation when compared with the Coflex, and they were declined by 34.53%, 57.86%, 75.81%, 25.21%; 36.22%, 67.31%, 75.01%, 71.40% compared with DIAM. The maximum stresses of the spinous process were 29.93 MPa, 24.66 MPa, 14.45 MPa, 24.37 MPa in the novel system, and those of Coflex and DIAM were 165.3 MPa, 109 MPa, 84.79 MPa, 47.66 MPa and 52.59 MPa, 48.78 MPa, 50.27 MPa, 44.16 MPa during the same condition. INTERPRETATION: Compared to other interspinous spacer devices, the novel interspinous fixation system demonstrated excellent stability, effectively distributing load on the intervertebral disc, and reducing the risk of spinous process fractures. The personalized design of the novel interspinous fixation system could be a viable option for treating degenerative disc diseases.

Different Load-Induced Alterations in Intervertebral Discs Between Low Back Pain Patients and Controls: A T2-map Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Investigate load-induced effects in lumbar intervertebral discs (IVDs) and differences between low back pain (LBP) patients and controls. SUMMARY OF BACKGROUND DATA: T2-map values, obtained from quantitative MRI sequences, reflect IVD tissue composition and integrity. Feasibility studies with T2-mapping indicate different load-induced effects in entire IVDs and posterior IVD parts between LBP patients and controls. Larger studies are required to confirm these findings and increase the understanding of specific characteristics distinguishing IVD changes in LBP patients compared with controls. MATERIALS AND METHODS: Lumbar IVDs of 178 patients (mean age: 43.8 yr; range: 20-60 yr) with >3 months of LBP and 74 controls (mean age: 40.3 yr; range: 20-60 yr) were imaged with T2-map sequence in a 3T scanner in supine position without axial load, immediately followed by a repeated examination, using the same sequence, with axial load. On both examinations, mean T2-map values were obtained from entire IVDs and from central/posterior IVD parts on the three midsagittal slices in 855 patient IVDs and 366 control IVDs. Load-induced effect was compared with Fold-change ratio and adjusted for IVD-degeneration grade. RESULTS: Loading induced an increase in T2-map values in both patients and controls. Excluding most extreme values, the ranges varied between -15% and +35% in patients and -11% and +36% in controls (first to 99th percentile). Compared with controls, the T2-map value increase in patients was 2% smaller in entire IVDs (Fold-change: 0.98, P =0.031), and for central and posterior IVD parts 3% (Fold-change: 0.98, P =0.005), respectively, 2% (Fold-change: 0.9, P =0.015) smaller. CONCLUSIONS: This quantitative study confirmed diverse load-induced behaviors between LBP patients and controls, suggesting deviant biomechanical characteristics between IVDs in patients and controls not only attributed to the global grade of degeneration. These findings are an important step in the continuous work of identifying specific IVD phenotypes for LBP patients. LEVEL OF EVIDENCE: Level II.

Decreased grip strength is associated with paraspinal muscular oxidative stress in female lumbar degenerative disease patients.

We aimed to investigate the relationship between superoxide dismutase 2-related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress. Patients were divided into two groups based on the superoxide dismutase 2 redox index. Spinal alignment, clinical skeletal muscle parameters, and succinic dehydrogenase (SDH) mean grayscale value were compared between the groups, with analyzes for both sexes. Multiple regression analyzes were used to adjust for the confounding effect of age on variables showing a significant difference between the two groups. Thirty-five patients with lumbar degenerative diseases were included. No significant differences were observed between the two groups for any of the parameters in males; however, females with a higher superoxide dismutase 2 redox index had greater lumbar lordosis, lower grip strength, and higher SDH mean grayscale value than those with a lower index. Multiple regression analyzes revealed that the superoxide dismutase 2 redox index was an independent explanatory variable for lumbar lordosis, grip strength, and SDH mean grayscale value in female patients. In conclusion, superoxide dismutase 2-related oxidative stress in the paraspinal muscles was associated with mitochondrial dysfunction and decreased grip strength in female lumbar degenerative disease patients.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Update on the Correlation Between Mitochondrial Dysfunction and Intervertebral Disk Degeneration.

Low back pain (LBP) is a common disorder in orthopedic outpatients, affecting people of all ages, and some patients may develop chronic LBP. As a complex organelle, mitochondria are not only energy workstations but also regulate cell senescence, apoptosis, and homeostasis. Mitochondrial dysfunction promotes disk degeneration by affecting a variety of pathophysiological processes, including oxidative stress, mitophagy, mitochondrial homeostasis, cellular senescence, and cell death. We review the molecular mechanisms underlying the relationship between mitochondrial dysfunction and intervertebral disk degeneration (IDD) to provide a theoretical basis for IDD treatment using pharmacological or tissue-engineering approaches.

Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells.

Intervertebral disk degeneration (IDD) is a major cause of low back pain that becomes a prevalent age-related disease. However, the pathophysiological processes behind IDD are rarely known. Here, we used bioinformatics analysis based on the microarray datasets (GSE34095) to identify the differentially expressed genes (DEGs) as biomarkers and therapeutic targets in degenerated discs. From the previous studies, oxidative stress has been notified as a positive inducement of IDD, which causes DNA damage and accelerates cell senescence. Polyamine oxidase (PAOX), a member of the observed 1057 DEGs, is involved in polyamine metabolism and influences the oxidative balance in cells. However, it is uncertain if the IDD is implicated in the dysregulation of PAOX and polyamine metabolism. This study firstly verified the PAOX upregulation in human degenerated disc samples and applied an IL-1ß-induced nucleus pulposus (NP) cell degeneration model to demonstrate that spermidine supplementation balanced polyamine metabolism and delayed NP cell senescence. Moreover, we confirmed that spermidine/N-acetylcysteine supplementation or Cdkn2a gene deletion stabilized the polyamine metabolism, suppressed oxidative stress, and therefore delayed the progress of IDD in older mice. Collectively, our study highlights the role of polyamine metabolism in IDD and foresees spermidine would be the advanced therapeutical drug for IDD.

G-Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species.

Intervertebral disc degeneration (IDD) is a chronic disease affecting millions of patients; however, its specific etiology is unknown. G protein-coupled receptors (GPRs) are a superfamily of integral membrane receptors in cells, and the receptors respond to a diverse range of stimuli and participate in multiple cellular activities. Here, using RNA-sequencing (RNA-seq) methods and immunohistochemistry, we revealed that G protein-coupled receptor 35 (GPR35) may have a relationship with IDD. Then, we demonstrated that the deletion of GPR35 in nucleus pulposus cells (NPCs) with siRNA or in Gpr35-/- mice significantly alleviated IDD caused by senescence or mechanical stress, further validating the pathological role of GPR35 in IDD. In addition, GPR35 induced the influx of Ca2+ and upregulation of reactive oxygen species (ROS) under mechanical stress in NPCs, which we believe to be the mechanism of GPR35-induced IDD. Finally, GPR35 caused upregulation of ROS in NPCs under mechanical stress, while excessive ROS stimulated the NPCs to express more GPR35 with a significant dose or time response. The u-regulated GPR35 could sense mechanical stress to produce more ROS and perpetuate this harmful cycle. In summary, our study shows that GPR35 plays a critical role in mediating IDD via mediating the influx of calcium ions and upregulating ROS, which implies a strong potential advantage of GPR35 as a prevention and treatment target in IDD.

Single-Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression.

Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures. The potential functional differences among NPC subpopulations are analyzed. Predictive transcripts, transcriptional factors, and signal pathways with respect to degeneration grades are explored. It is reported that fibroNPCs is the subpopulation for end-stage degeneration. CD90+NPCs are observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). Integrin αM (CD11b) and oxidized low density lipoprotein receptor 1 (OLR1) as surface markers of NP-derived G-MDSCs are uncovered. The G-MDSCs are found to be enriched in mildly degenerated (grade II and III) NP tissues compared to severely degenerated (grade IV and V) NP tissues. Their immunosuppressive function and alleviation effects on NPCs' matrix degradation are revealed in vitro. Collectively, this study reveals the NPC-type complexity and phenotypic characteristics in NP, thereby providing new insights and clues for IVDD treatment.