Disc Degeneration Research Articles

Evaluation of the Thickness of Ligamentum Flavum at the Level of Lumbosacral Spine (L4-L5, L5-S1) and its Relationship with Degenerative Disc Changes in Patients Undergoing MRI of Lumbosacral Spine

Introduction: Low back pain (LBP) is a very common cause of disability in working-age adults; with degenerative changes being the predominant cause apart from anatomical factors. Degenerative changes in the lumbar spine are associated with the alteration of the thickness of the Ligamentum Flavum (LF), which predisposes to clinical symptoms. Methods: This was a prospective study conducted among ninety symptomatic (LBP) patients who underwent magnetic resonance imaging (MRI) and the images were evaluated to measure the thickness of the LF and evaluate the degree of disc degeneration by the Pfirrmann grading system, according to the spinal levels (L4-L5, L5-S1). An association was sought between LF hypertrophy and disc degeneration, age, sex, and disc height. Results: The result of this study showed that with increasing age thickening of the LF could lead to degeneration of the intervertebral disc. Thickening of the LF was more at the level of L4-L5 level than at the L5-S1 level with right-sided increased thickness more than on the left and is associated with increased grade of disc degeneration. Females had slightly more thickened LF than the males at the L4-L5 level with no gender predominance at the L5-S1 level. Conclusions: Thickening of the ligamentum flavum may be an important factor in the origin of LBP, especially in the adult population. A degenerative process in the ligamentum flavum that occurs with age and also suggests the thickening of LF due to mechanical stress at the lumbar level would ultimately result in degeneration of the disc.

Comparison of histopathologic findings of initial and recurrent lumbar disc herniation

Objective: Recurrent lumbar disc hernia (RLDH) is a common and challenging complication after an initial discectomy. This study aimed to investigate the relationship between the histopathologic outcomes of the initial and recurrent disc tissues. Methods: This study investigated 70 patients who underwent a microdiscectomy and subsequently developed same-level same-side lumbar disc herniation (LDH) recurrence. The clinic, western blot, and immunohistochemical evaluations of patients with initial LDH and RLDH were conducted and statistically analyzed. Results: The effect of inflammation and apoptosis in the degenerative changes of intervertebral disc hernia and increased histopathologic findings in RLDH was demonstrated. The degeneration of the hernia disc tissue is a major pathological process, which is characterized by cellular apoptosis, inflammation, and reduced synthesis of extracellular matrix. Currently, there is no clinical therapy targeting the reversal of disc degeneration. Conclusions: This, therefore, stay away from factors that increase inflammation in the intervention of intervertebral disc hernia, applying to reduce inflammation the medicines, could allow reducing disc collagen degeneration, and more successful outcomes. These findings might shed some new lights on the mechanism of disc degeneration and provide new strategies for the treatments of initial and recurrent LDH.

S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells.

Sphingosine 1-phosphate receptor 3 (S1PR3) participates in the inflammatory response in multiple types of diseases. However, the biological role of S1PR3 in intervertebral disc degeneration and the underlying mechanism are unclear. The aim of the present study was to investigate the functional role and the mechanism of S1PR3 in lipopolysaccharide (LPS)-induced human nucleus pulposus cells. The expression of S1PR3 and Toll-like receptor (TLR) 2 in LPS-induced nucleus pulposus (NP) cells was investigated using western blotting. The Cell Counting Kit-8 assay was used to detect cell proliferation, and the levels of inflammatory factors were detected using ELISA. Flow cytometry and western blotting were used for the assessment of apoptosis. The deposition of extracellular matrix (ECM) proteins was investigated using reverse transcription-quantitative PCR and western blotting. In addition, western blotting was used to investigate the protein expression levels of phosphorylated (p)-STAT3, STAT3, p-JNK, JNK, p-ERK, ERK, p-p38 and p38associated with STAT3 and MAPK signaling. S1PR3 expression was reduced, while TLR2 expression was elevated in LPS-induced human nucleus pulposus cells (HNPC). S1PR3 overexpression increased HNPC viability, inhibited the inflammatory response and suppressed apoptosis. Meanwhile, S1PR3 overexpression regulated the expression of ECM-related proteins. Additionally, overexpression of S1PR3 inhibited the expression of the TLR2-regulated STAT3 and MAPK pathways in LPS-induced HNPCs. Furthermore, TLR2 overexpression partially offset the impacts of S1PR3 overexpression on HNPC viability, apoptosis level, inflammation and as ECM degradation. In conclusion, STAT3 overexpression suppressed viability injury, the inflammatory response and the level of apoptosis and alleviated ECM protein deposition in HNPCs through the TLR2/STAT3 and TLR2/MAPK pathways, which may offer a promising candidate for the amelioration of intervertebral disc degeneration.

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m6A regulator can be classified into three types, namely the "writer", "reader", and "eraser". Studies have shown that the epigenetic modulation of m6A influences mRNA processing, nuclear export, translation, and splicing. Regulated cell death (RCD) is the autonomous and orderly death of cells under genetic control to maintain the stability of the internal environment. Moreover, distorted RCDs are widely used to influence the course of various diseases and receiving increasing attention from researchers. In the past few years, increasing evidence has indicated that m6A can regulate gene expression and thus influence different RCD processes, which has a central role in the etiology and evolution of MSDs. The RCDs currently confirmed to be associated with m6A are autophagy-dependent cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic cell death, NETotic cell death and oxeiptosis. The m6A-RCD axis can regulate the inflammatory response in chondrocytes and the invasive and migratory of MM cells to bone remodeling capacity, thereby influencing the development of MSDs. This review gives a complete overview of the regulatory functions on the m6A-RCD axis across muscle, bone, and cartilage. In addition, we also discuss recent advances in the control of RCD by m6A-targeted factors and explore the clinical application prospects of therapies targeting the m6A-RCD in MSD prevention and treatment. These may provide new ideas and directions for understanding the pathophysiological mechanism of MSDs and the clinical prevention and treatment of these diseases.

Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.

Aims: Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. Results: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both ex vivo and invivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. Innovation and Conclusions: A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.

OA29 Epigenetic regulation of IL-4 promoter targeting p300 attenuating intervertebral disc degeneration and pain by inhibiting IL-1β

Abstract Background/Aims Low back pain (LBP) is a prevalent condition primarily caused by intervertebral disc degeneration (IVDD), which imposes a substantial social and medical burden. Effective targeted treatments to prevent the progression of IVDD and alleviate LBP are still lacking. p300, a critical member of the histone acetyltransferase (HAT) family, is involved in the regulation of inflammation. This study aims to investigate the role of p300/IL-4 in IVDD and pain and elucidate the underlying molecular mechanism. Methods Human intervertebral disc samples were collected and graded based on the Pfirrmann grading scheme. A rat model of IVDD was established through posterior disc puncture, and various treatments were administered. Human nucleus pulposus cells (NPCs) were isolated and cultured, followed by assessments including qRT-PCR, Western blotting, immunofluorescence, and histopathological analyses. The mechanical and thermal hyperalgesia were assessed using von Frey hair tests and the plantar test, respectively. Chromatin immunoprecipitation (ChIP) and ChIP-qPCR were performed, and lentivirus transduction was used for p300 knockdown. Results We investigated the role of CREB binding protein (CBP)/p300 in IVDD. Degenerated nucleus pulposus (NP) tissues from IVDD patients exhibited a significant downregulation of p300 at both nucleic acid and protein levels, while CBP levels remained unchanged. Manipulating p300 expression in NPCs regulated matrix production, with p300 overexpression enhancing aggrecan and collagen II expression and knockdown leading to increased matrix-degrading proteins. In a rat IVDD model, activating p300 function with CTPB (p300-specific activator) alleviated IVDD and pain, while inhibiting p300 with C646 exacerbated IVDD and pain. Transcriptome analysis implicated IL-4 as a downstream effector of p300, and IL-4 demonstrated protective effects against IVDD and pain. Mechanistically, p300 was found to acetylate H3K27 at the IL-4 promoter, promoting its expression. Conclusion The novel findings of this study suggest that the p300/IL-4/IL-1β axis may represent a promising therapeutic target for IVDD and LBP. These results propose a hypothesis that, early in the inflammatory phase, NPCs may initiate a self-protective mechanism through p300, aiding itself in preserving a favourable metabolic microenvironment. This mechanism is primarily mediated by the expression of IL-4, which has the capacity to counteract IL-1β, rather than TNF-α. Disclosure H. Cui: None. Z. Zheng: None.

Percutaneous endoscopic lumbar discectomy combined with platelet-rich plasma injection for lumbar disc herniation: analysis of clinical and imaging outcomes

ObjectiveTo evaluate the clinical efficacy and imaging outcomes of percutaneous endoscopic lumbar discectomy (PELD) combined with platelet-rich plasma (PRP) for the treatment of lumbar disc herniation (LDH).MethodsA total of 155 patients with LDH between January 2020 and June 2022 were retrospective analyzed, of which 75 underwent PELD with PRP and 80 underwent PELD only. Clinical functional scores and imaging data were compared. Clinical functional scores included visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), Japanese Orthopedic Association score (JOA), Oswestry Disability Index (ODI) and modified MacNab criteria. Imaging data included disc height index (DHI), spinal cross-sectional area (SCSA), disc protrusion size (DPZ), and ratio value of disc grey scales (RVG).ResultsBoth groups showed clinical improvement, and VAS-LP, VAS-BP, JOA and ODI were significantly improved in the PRP group compared with the control group at 3, 6 and 12 months postoperatively (P < 0.05). At the last follow-up, the differences in SCSA, DPZ and RVG between the two groups were statistically significant (P < 0.05), with the PRP group being superior to the control group. The excellent and good rates of the modified Macnab criteria in the PRP group and control group were 93.3% and 90%, respectively, with no statistically significant difference (P > 0.05). No serious complications occurred during the follow-up period.ConclusionPELD combined with PRP is a safe and effective method for treating patients with LDH. PRP injection was beneficial for delaying disc degeneration and promoting disc remodeling.

Single-cell RNA-seq analysis reveals the Wnt/Ca2+ signaling pathway with inflammation, apoptosis in nucleus pulposus degeneration

BackgroundIncreasing studies have shown degeneration of nucleus pulposus cells (NPCs) as an critical part of the progression of intervertebral disc degeneration (IVDD). However, there are relatively few studies on single-cell transcriptome contrasts in human degenerated NPCs. Moreover, differences in Wnt/Ca2+ signaling in human degenerated nucleus pulposus cells have not been elucidated. The aim of this study is to investigate the differential expression of Wnt/Ca2+ signaling pathway between normal and degenerated nucleus pulposus cells in humans and try to investigate its mechanism.MethodsWe performed bioinformatics analysis using our previously published findings to construct single cell expression profiles of normal and degenerated nucleus pulposus. Then, in-depth differential analysis was used to characterize the expression of Wnt/Ca2+ signaling pathway between normal and degenerated nucleus pulposus cells in humans.ResultsThe obtained cell data were clustered into five different chondrocytes clusters, which chondrocyte 4 and chondrocyte 5 mainly accounted for a high proportion in degenerated nucleus pulposus tissues, but rarely in normal nucleus pulposus tissues. Genes associated within the Wnt/Ca2+ signaling pathway, such as Wnt5B, FZD1, PLC (PLCB1), CaN (PPP3CA) and NAFATC1 are mainly present in chondrocyte 3, chondrocyte 4 and chondrocyte 5 from degenerated nucleus pulposus tissues. In addition, as a receptor that activates Wnt signaling pathway, LRP5 is mainly highly expressed in chondrocyte 5 of degenerated nucleus pulposus cells. Six genes, ANGPTL4, PTGES, IGFBP3, GDF15, TRIB3 and TNFRSF10B, which are associated with apoptosis and inflammatory responses, and are widespread in chondrocyte 4 and chondrocyte 5, may be closely related to degenerative of nucleus pulposus cells.ConclusionsSingle-cell RNA sequencing revealed differential expression of Wnt/Ca2+ signaling in human normal and degenerated nucleus pulposus cells, and this differential expression may be closely related to the abundance of chondrocyte 4 and chondrocyte 5 in degenerated nucleus pulposus cells. In degenerated nucleus pulposus cells, LRP5 activate Wnt5B, which promotes nucleus pulposus cell apoptosis and inflammatory response by regulating the Wnt/Ca2+ signaling pathway, thereby promoting disc degeneration. ANGPTL4, IGFBP3, PTGES in chondrocyte 4 and TRIB3, GDF15, TNFRSF10B in chondrocyte 5 may play an important role in this process.

Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk.

Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

Practice variation in surgical treatment for lumbar degenerative disc disease: exploring regional and hospital factors influencing surgical rates

The presence of significant, unwarranted variation in treatment suggests that clinical decision making also depends on where patients live instead of what they need and prefer. Historically, high practice variation in surgical treatment for lumbar degenerative disc disease (LDDD) has been documented. This study aimed to investigate current regional variation in surgical treatment for sciatica resulting from LDDD. We conducted a retrospective, cross-sectional analysis of all Dutch adults (>18 years) between 2016 and 2019. Demographic data from Statistics Netherlands were merged with a nationwide claims database, covering over 99% of the population. Inclusion criteria comprised LDDD diagnosis codes and relevant surgical codes. Practice variation was assessed at the level of postal code areas and hospital service areas (HSAs). Multivariable logistic regression analysis was employed to identify variables associated with surgical treatment. Among the 119,148 hospital visitors with LDDD, 14,840 underwent surgical treatment. Practice variation for laminectomies and discectomies showed less than two-fold variation in both postal code and HSAs. However, instrumented fusion surgery demonstrated a five-fold variation in postal code areas and three-fold variation in HSAs. Predictors of receiving surgical treatment included opioid prescription and patient referral status. Gender differences were observed, with males more likely to undergo laminectomy or discectomy, and females more likely to receive instrumented fusion surgery. Our study revealed low variation rates for discectomies and laminectomies, while indicating a high variation rate for instrumented fusion surgery in LDDD patients. High-quality research is needed on the extent of guideline implementation and its influence on practice variation.

Intervertebral disc degeneration instigates vertebral endplate remodeling and facet joint pathology in a large animal model

Intervertebral disc degeneration instigates vertebral endplate remodeling and facet joint pathology in a large animal model

Regulation of endoplasmic reticulum stress on autophagy and apoptosis of nucleus pulposus cells in intervertebral disc degeneration and its related mechanisms.

Intervertebral disc degeneration (IVDD) is a common and frequent disease in orthopedics, which seriously affects the quality of life of patients. Endoplasmic reticulum stress (ERS)-regulated autophagy and apoptosis play an important role in nucleus pulposus (NP) cells in IVDD. Hypoxia and serum deprivation were used to induce NP cells. Cell counting kit-8 (CCK-8) assay was used to detect cell activity and immunofluorescence (IF) was applied for the appraisement of glucose regulated protein 78 (GRP78) and green fluorescent protein (GFP)-light chain 3 (LC3). Cell apoptosis was detected by flow cytometry and the expression of LC3II/I was detected by western blot. NP cells under hypoxia and serum deprivation were induced by lipopolysaccharide (LPS), and intervened by ERS inhibitor (4-phenylbutyric acid, 4-PBA) and activator (Thapsigargin, TP). Then, above functional experiments were conducted again and western blot was employed for the evaluation of autophagy-, apoptosis and ERS-related proteins. Finally, NP cells under hypoxia and serum deprivation were stimulated by LPS and intervened using apoptosis inhibitor z-Val-Ala-DL-Asp-fluoromethyl ketone (Z-VAD-FMK) and autophagy inhibitor 3-methyladenine (3-MA). CCK-8 assay, IF, flow cytometry and western blot were performed again. Besides, the levels of inflammatory cytokines were measured with enzyme-linked immunosorbent assay (ELISA) and the protein expressions of programmed death markers were estimated with western blot. It showed that serum deprivation induces autophagy and apoptosis. ERS was significantly activated by LPS in hypoxic and serum deprivation environment, and autophagy and apoptosis were significantly promoted. Overall, ERS affects the occurrence and development of IVDD by regulating autophagy, apoptosis and other programmed death.

Quantification of the Water Content of Human Intervertebral Discs in Various Regions and Conditions

Background: Intervertebral disc (IVD) water is a basic factor for modeling tissue growth and nutritional diffusion and its amount is directly related to the development of degenerative processes. Objective: direct assessment of human IVD water contents in different disc regions in correlation to age and disc degeneration processes. Methods: 103 IVD samples that were taken from 30 cadavers underwent a lyophilization process to assess their water contents. The results were tabulated and tested statistically in relation to different parameters, including gender, age, spinal level and degeneration grading. Results: This study reveals that the water content was significantly lower in the group whose age was more than the median age (83 years) when compared with the group whose age was less than the median age. Additionally, the study shows that the water content is dramatically and significantly reduced in individuals who have degenerative changes. Conclusions: The water content of the intervertebral disc directly correlates with age and the degeneration process, decreasing as age and degeneration progress.

Dynamics of CD44+ bovine nucleus pulposus cells with inflammation

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors. CD44 widespread expression in NP was partially associated with CD14 and CD45, resulting in the identification of distinct cell subsets. In conclusion, this study points out CD44 and CD44-based cell subsets as relevant targets in the modulation of the IVD pro-inflammatory/degenerative cascade.

Osteoporosis treatments for intervertebral disc degeneration and back pain: a perspective.

Low back pain derived from intervertebral disc (IVD) degeneration is a debilitating spinal condition that, despite its prevalence, does not have any intermediary guidelines for pharmacological treatment between palliative care and invasive surgery. The development of treatments for the IVD is complicated by the variety of resident cell types needed to maintain the regionally distinct structural properties of the IVD that permit the safe, complex motions of the spine. Osteoporosis of the spine increases the risk of vertebral bone fracture that can increase the incidence of back pain. Fortunately, there are a variety of pharmacological treatments for osteoporosis that target osteoblasts, osteoclasts and/or osteocytes to build bone and prevent vertebral fracture. Of particular note, clinical and preclinical studies suggest that commonly prescribed osteoporosis drugs like bisphosphonates, intermittent parathyroid hormone, anti-sclerostin antibody, selective estrogen receptor modulators and anti-receptor activator of nuclear factor-kappa B ligand inhibitor denosumab may also relieve back pain. Here, we cite clinical and preclinical studies and include unpublished data to support the argument that a subset of these therapeutics for osteoporosis may alleviate low back pain by also targeting the IVD.

Risk Factors for Surgical Treatment of Lumbar Degenerative Disc Disease in Middle-aged and Older Women: A Prospective Case-Control Study of 2370 Subjects.

Given the distinct physiological and societal traits between women and men, we propose that there are distinct risk factors for lumbar degenerative disc disease surgeries, including lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS), in middle-aged and older populations. However, few studies have focused on middle-aged and older women. This study aims to identify these risk factors specifically in this population. In this case-control study, the study group comprised 1202 women aged ≥ 45 years who underwent operative treatment of lumbar degenerative disc disease (LDH, n = 825; LSS, n = 377), and the control group comprised 1168 women without lumbar disease who visited a health examination clinic during the same period. The study factors included demographics (age, body mass index [BMI], smoking, labor intensity, and genetic history), female-specific factors (menopausal status, number of deliveries, cesarean section, and simple hysterectomy), surgical history (number of abdominal surgeries, hip joint surgery, knee joint surgery, and thyroidectomy), and systemic diseases (hypercholesterolemia, hypertriglyceridemia, hyper-low-density lipoprotein cholesterolemia, hypertension, diabetes, cardiovascular disease, and cerebrovascular disease). Multivariate binary logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of associated factors. The risk factors for surgical treatment of LDH in middle-aged and older women included BMI (OR = 1.603), labor intensity (OR = 1.189), genetic history (OR = 2.212), number of deliveries (OR = 1.736), simple hysterectomy (OR = 2.511), hypertriglyceridemia (OR = 1.932), and hyper-low-density lipoprotein cholesterolemia (OR = 2.662). For surgical treatment of LSS, the risk factors were age (OR = 1.889), BMI (OR = 1.671), genetic history (OR = 2.134), number of deliveries (OR = 2.962), simple hysterectomy (OR = 1.968), knee joint surgery (OR = 2.527), hypertriglyceridemia (OR = 1.476), hyper-low-density lipoprotein cholesterolemia (OR = 2.413), and diabetes (OR = 1.643). Cerebrovascular disease was a protective factor against surgery for LDH (OR = 0.267). BMI, genetic history, number of deliveries, simple hysterectomy, hypertriglyceridemia, and hyper-low-density lipoprotein cholesterolemia were independent risk factors for surgical treatment of both LDH and LSS in middle-aged and older women. Two disparities were found: labor intensity was a risk factor for LDH patients, and knee joint surgery and diabetes were risk factors for LSS patients.

Radiographic and surgery-related predictive factors for increased segmental lumbar lordosis following lumbar fusion surgery in patients with degenerative lumbar spondylolisthesis.

This study aimed to evaluate preoperative (pre-op) radiographic characteristics and specific surgical interventions in patients with degenerative lumbar spondylolisthesis (DLS) who underwent lumbar fusion surgery (LFS), with a focus on analyzing predictors of postoperative restoration of segmental lumbar lordosis (SLL). A retrospective review at a single center identified consecutive single-level DLS patients who underwent LFS between 2016 and 2022. Radiographic measures included disc angle (DA), SLL, lumbar lordosis (LL), anterior/posterior disc height (ADH/PDH), spondylolisthesis percentage (SP), intervertebral disc degeneration, and paraspinal muscle quality. Surgery-related measures included cage position, screw insertion depth, spondylolisthesis reduction rate, and disc height restoration rate. A change in SLL ≥ 4° indicated increased segmental lumbar lordosis (ISLL), and unincreased segmental lumbar lordosis (UISLL) < 4°. Propensity score matching was employed for a 1:1 match between ISLL and UISLL patients based on age, gender, body mass index, smoking status, and osteoporosis condition. A total of 192 patients with an average follow-up of 20.9months were enrolled. Compared to UISLL patients, ISLL patients had significantly lower pre-op DA (6.78° vs. 11.84°), SLL (10.73° vs. 18.24°), LL (42.59° vs. 45.75°), and ADH (10.09mm vs. 12.21mm) (all, P < 0.05). ISLL patients were predisposed to more severe intervertebral disc degeneration (P = 0.047) and higher SP (21.30% vs. 19.39%, P = 0.019). The cage was positioned more anteriorly in ISLL patients (67.00% vs. 60.08%, P = 0.000), with more extensive reduction of spondylolisthesis (- 73.70% vs. - 56.16%, P = 0.000) and higher restoration of ADH (33.34% vs. 8.11%, P = 0.000). Multivariate regression showed that lower pre-op SLL (OR 0.750, P = 0.000), more anterior cage position (OR 1.269, P = 0.000), and a greater spondylolisthesis reduction rate (OR 0.965, P = 0.000) significantly impacted SLL restoration. Pre-op SLL, cage position, and spondylolisthesis reduction rate were identified as significant predictors of SLL restoration after LFS for DLS. Surgeons are advised to meticulously select patients based on pre-op SLL and strive to position the cage more anteriorly while minimizing spondylolisthesis to maximize SLL restoration.

Automatic grading of intervertebral disc degeneration in lumbar dog spines.

Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients. MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images. The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades. The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.

Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy.

Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro. In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models. In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model. API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

The Role of Immunocyte Infiltration Regulatory Network Based on hdWGCNA and Single-Cell Bioinformatics Analysis in Intervertebral Disc Degeneration

The Role of Immunocyte Infiltration Regulatory Network Based on hdWGCNA and Single-Cell Bioinformatics Analysis in Intervertebral Disc Degeneration