Lumbar vertebral endplates lesions (LEPLs), one of the etiologies of low back pain (LBP), are one of the most prevalent causes of health-care costs. Despite progressively becoming the focus in recent ...years, almost all studies have concentrated on symptomatic patients rather than general populations. As a result, our study was designed to determine the prevalence and distribution patterns of LEPLs in a middle-young general population, as well as their associations with lumbar disc herniation (LDH), lumbar disc degeneration (LDD), and lumbar vertebral volumetric bone mineral density (vBMD).
Seven hundred fifty-four participants aged 20-60 years were recruited from the subjects enrolled in a 10-year longitudinal study of degeneration of the spine and knee being conducted at the Beijing Jishuitan Hospital and 4 of them were excluded due to the missing of MRIs. In this observational study, a lumbar quantitative computed tomography (QCT) and MRI scan were performed among participants within 48 h. T2-weighted sagittal lumbar MRI images for all included subjects were identified for LEPLs by two independent observers based on morphological and local characteristics. Lumbar vertebral vBMD was measured with QCT. The age, BMI, waistline, hipline, lumbar vBMD, LDD, and LDH were measured to investigate their associations with LEPLs.
The prevalence of LEPLs was higher among the male subjects. 80% of endplates were recognition as no lesions with a substantial disparity between female (75.6%) and male subjects (83.4%) (p < 0.001). The most common lesions were "wavy/irregular" and "notched", and "fracture" is most involved in L3-4 inferior endplate both in two genders. LEPLs were found to be associated with LDH (≥ 2 levels: OR = 6.859, P < 0.001; 1 level: OR = 2.328, P = 0.002 in men. OR = 5.004, P < 0.001; OR = 1.805, P = 0.014 in women) reference for non-LDH, and hipline in men (OR = 1.123, P < 0.001).
LEPLs are the common findings on lumbar MRIs in general population, particularly in men. The presence of these lesions and advance from slightly to severely could be mainly attributed to LDH and men's higher hipline.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell ...homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD.
Purpose
High intensity zones (HIZ) in the lumbar intervertebral disk (IVD) can be associated with degenerative changes which may ultimately manifest as low back pain (LBP). However, the relationship ...between the prevalence of HIZ and lumbar degenerative parameters is still unclear. The purpose of this study was to determine the prevalence of HIZ in the lumbar spine, analyze the independent relationship between HIZ and lumbar degenerative parameters measured on MRI and X-ray and determine the association between HIZ and the presence of LBP.
Methods
A retrospective review of MRI data, X-ray data, and radiology reports for 136 consecutively recruited patients, above 18-years-age and with both lumbar MRI and X-ray scans was conducted. 57 patients with HIZ were identified. Patients without HIZ (n = 79) made up the control group.
Results
HIZ was prevalent in 41.9% of patients and in 11.0% of all lumbar IVDs. The odds of developing HIZ were 6.4 (Exp(B) 6.4, 95%CI 3.157–12.988) and 3.0 (Exp(B) 3.0, 95%CI 1.603, 5.674) times higher in IVDs with disk bulge/protrusion and nucleus degeneration, respectively. Odds of HIZ was also increased in disks with larger IVD angle (Exp(B) 1.1, 95%CI 1.034, 1.169). The odds of patients presenting to imaging with LBP was 3.0 (OR 3.0, 95%CI 1.478–6.338) times higher in the HIZ compared to the control group.
Conclusions
HIZ was prevalent in 41.9% of participants that were recruited in this study. Nucleus degeneration, disk bulge/protrusion and increased IVD angle were found to be independently associated with HIZ and since there is an increased likelihood of LBP, we posit that HIZ is likely a symptomatic and clinically meaningful diagnostic tool in the assessment of LBP.
Intervertebral disc degeneration (IVDD) is a common degenerative condition leading to abnormal stress distribution under load, causing intervertebral stenosis, facet joint degeneration, and foraminal ...stenosis. Very little is known about the molecular mechanism of eRNAs in IVDD.
Gene expression profiles of 38 annulus disc samples composed of 27 less degenerated discs (LDs) and 11 more degenerated discs (MDs) were retrieved from the GEO database. Then, differentially expressed enhancer RNAs (DEeRNAs), differentially expressed target genes (DETGs), and differentially expressed transcription factors (DETFs), hallmark of cancer signalling pathways according to GSVA; the types and quantity of immune cells according to CIBERSORT; and immune gene sets according to ssGSEA were analysed to construct an IVDD-related eRNA network. Then, multidimensional validation was performed to explore the interactions among DEeRNAs, DETFs and DEGs in space.
A total of 53 components, 14 DETGs, 15 DEeRNAs, 3 DETFs, 5 immune cells, 9 hallmarks, and 7 immune gene sets, were selected to construct the regulatory network. After validation by online multidimensional databases, 21 interactive DEeRNA-DEG-DETF axes related to IVDD exacerbation were identified, among which the C1S-CTNNB1-CHD4 axis was the most significant.
Based upon the results of our study, we theorize that the C1S-CTNNB1-CHD4 axis plays a vital role in IVDD exacerbation. Specifically, C1S recruits CTNNB1 and upregulates the expression of CHD4 in IVDD, and subsequently, CHD4 suppresses glycolysis and activates oxidative phosphorylation, thus generating insoluble collagen fibre deposits and leading to the progression of IVDD. Overall, these DEeRNAs could comprise promising therapeutic targets for IVDD due to their high tissue specificity.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to ...IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA sequencing of non-degenerated and degenerated CEP cells were performed.
Human lumbar CEP cells from degenerated (Thompson grade ≥ 4) and non-degenerated (Thompson grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA sequencing. Genes identified from bulk RNA sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples.
Bulk RNA sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells, and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA sequencing dataset showed that progenitor cell clusters from both samples were enriched in "non-degenerated" genes but not "degenerated" genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction.
This thorough analysis using RNA sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk ...healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing.
Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disc function after injury, the basic biology underlying intervertebral disc healing remains poorly understood. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment, and describes the.spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells.
As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc ...degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.
Intervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP). IVD herniation involves cellular and extracellular matrix (ECM) ...alterations that have been associated with tissue fibrosis, although still poorly investigated.
Here, fibrotic alterations in human AF were evaluated, by characterizing the herniated ECM. Human AF samples (herniated lumbar IVD (n = 39, age 24-83) and scoliosis controls (n = 6, age 15-21)) were processed for transmission electron microscopy and histological/immunohistochemical analysis of fibrotic markers. Correlations between the fibrotic markers in AF ECM and the degree of NP containment (protused, contained and uncontained) and patients' age were conducted.
Our results demonstrate that with herniation progression, i.e. loss of NP containment, human AF presents less stained area of sulphated glycosaminoglycans and collagen I, being collagen I fibres thinner and disorganized. On the other hand, fibronectin stained area and percentage of α-smooth muscle actin+ cells increase in human AF, while matrix metalloproteinase-12 (MMP12) production and percentage of macrophages (CD68+ cells) remain constant. These structural and biochemical fibrotic alterations observed in human AF with herniation progression occur independently of the age.
The characterization of human AF here conducted evidence the presence of fibrosis in degenerated IVD, while highlighting the importance of considering the herniation progression stage, despite the patients' age, for a better understanding of the mechanisms behind AF failure and IVD herniation.
Percutaneous endoscopic lumbar discectomy (PELD) is a relatively safe and effective minimally invasive surgery in the treatment of calcified lumbar disc herniation (CLDH). However, studies on ...percutaneous endoscopic interlaminar discectomy (PEID) and percutaneous endoscopic transforaminal discectomy (PETD) for CLDH have rarely been reported. This research aimed to compare the clinical efficacy of PEID and PETD for L5-S1 CLDH.
We retrospectively analyzed 54 consecutive patients with L5-S1 CLDH treated with PELD at our institution from August 2016 to August 2020. Patients were divided into PEID group (n = 28) and PETD (n = 26) group according to the surgical methods. The demographic characteristics and surgical results of the two groups were compared. Clinical outcomes were estimated by the visual analog scale (VAS) for leg pain, Oswestry disability index (ODI) and modified MacNab criteria.
All patients were successfully operated on by PEID or PETD. No significant differences in the demographic characteristics, intraoperative blood loss, postoperative hospital stay and complication rate were noted between the PEID and PETD groups. The excellent and good rates in the PEID group were similar to those in the PETD group (89.29% vs 88.46%, P = 1.000), whereas the PEID group exhibited superior results for operative time (min) (64.61 ± 5.60 vs 85.58 ± 8.52, P < 0.001) and fluoroscopy times (n) (2.93 ± 0.90 vs 13.35 ± 2.30, P < 0.001) compared with the PETD group.
PEID has achieved good clinical efficacy as PETD for L5-S1 CLDH. Compared with PETD, PEID has the advantages of shorter operative time and a reduced number of fluoroscopy times in the treatment of CLDH.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Percutaneous transforaminal endoscopy has been widely used to treat lumbar disc herniation (LDH), but the steep learning curve and difficulties in removing the calcified disc hinders the application ...of conventional endoscopy in treating calcified lumbar disc herniation (CLDH). In 2017, we first reported Percutaneous Transforaminal Endoscopic Surgery (PTES) as an easy-to-learn posterolateral transforaminal endoscopic technique to decompress the nerve root for LDH. We used our PTES technique to remove the calcified LDH and the purpose of this study is to evaluate the safety and efficacy of this technique.
Forty-six patients with CLDH and fifty-five patients with uncalcified lumbar disc herniation (ULDH) underwent PTES to decompress the nerve root. Visual analogue scale was collected before the surgery, immediately, one week, one month, two months, three months, six months, 12 months and 24 months after surgery. The outcomes of MacNab classification were collected 24 months after surgery. Intra- and Post-operative complications were also recorded.
For CLDH patients, the VAS score was 9 (5-10) before operation, and then dropped to 2 (1-4) after surgery. VAS score continually decreased to 0 (0-3) at 24 months after surgery. 95.65% of CLDH patients showed excellent or good outcomes. ULDH group showed similar MacNab classification (94.55%) and VAS changing curve. The therapeutic effect of PTES in treating CLDH was as good as that in treating uncalcified patients.
PTES is an effective and safe method to treat calcified lumbar disc herniation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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