New perspectives on YTHDF2 O-GlcNAc modification in the pathogenesis of intervertebral disc degeneration.

This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.

[Effects of Oxidative Stress on Mitochondrial Functions and Intervertebral Disc Cells]. / 氧化应激对线粒体功能及椎间盘细胞的影响.

Intervertebral disc degeneration is widely recognized as one of the main causes of lower back pain. Intervertebral disc cells are the primary cellular components of the discs, responsible for synthesizing and secreting collagen and proteoglycans to maintain the structural and functional stability of the discs. Additionally, intervertebral disc cells are involved in maintaining the nutritional and metabolic balance, as well as exerting antioxidant and anti-inflammatory effects within the intervertebral discs. Consequently, intervertebral disc cells play a crucial role in the process of disc degeneration. When these cells are exposed to oxidative stress, mitochondria can be damaged, which may disrupt normal cellular function and accelerate degenerative changes. Mitochondria serve as the powerhouse of cells, being the primary energy-producing organelles that control a number of vital processes, such as cell death. On the other hand, mitochondrial dysfunction may be associated with various degenerative pathophysiological conditions. Moreover, mitochondria are the key site for oxidation-reduction reactions. Excessive oxidative stress and reactive oxygen species can negatively impact on mitochondrial function, potentially leading to mitochondrial damage and impaired functionality. These factors, in turn, triggers inflammatory responses, mitochondrial DNA damage, and cell apoptosis, playing a significant role in the pathological processes of intervertebral disc cell degeneration. This review is focused on exploring the impact of oxidative stress and reactive oxygen species on mitochondria and the crucial roles played by oxidative stress and reactive oxygen species in the pathological processes of intervertebral disc cells. In addition, we discussed current cutting-edge treatments and introduced the use of mitochondrial antioxidants and protectants as a potential method to slow down oxidative stress in the treatment of disc degeneration.

Influence of the preoperative L5S1 disc state on lateral L2 to L5 fusion's outcomes at an average follow-up of 3,5 years (minimum 2 years).

INTRODUCTION: The impact of pre-existing degeneration of a disc underlying a lumbar arthrodesis via lateral approach on long-term clinical outcome has, to our knowledge, not been studied. When performing arthrodesis between L2 and L5, its extension to L5S1 is challenging because it imposes a different surgical approach. Therefore, surgeon's temptation is to not include L5S1 in the fusion even in case of discopathy. Our objective was to study the influence of the preoperative L5S1 status on the clinical outcome of lumbar lateral interbody fusion (LLIF) using a pre-psoatic approach between L2 and L5 with a minimum follow-up of 2 years. MATERIAL AND METHODS: Patients who underwent LLIF from L2 to L5 between 2015 and 2020 were included in our study. We studied VAS, ODI, and global clinical outcome before surgery and at last follow-up. The L5-S1 disc was radiologically studied in preoperative imaging. Patients were included in two groups (A "with" and B :without" L5-S1 disc degeneration) to compare the clinical outcomes at last follow-up. Our primary objective was to evaluate the rate of L5-S1 disc revision surgery at last follow-up. RESULTS: 102 patients were included. 2 required L5-S1 disc surgery following overlying arthrodesis. Our results showed a significant improvement in the patients' clinical outcomes at the last follow-up (p < 0.0001). We did not find any significant difference on clinical criteria between groups A & B. CONCLUSION: A preop L5S1 disc degeneration does not seem to impact the final clinical outcomes after lumbar lateral interbody fusion at a minimal two years F.U. It should not be systematically involved in an overlying fusion.

The Use of Medical Ozone in Chronic Intervertebral Disc Degeneration Can Be an Etiological and Conservative Treatment.

Degeneration of the intervertebral disc is one of the most frequent causes of lumbar pain, and it puts an extreme strain on worldwide healthcare systems. Finding a solution for this disease is an important challenge as current surgical and conservative treatments fail to bring a short-term or long-term solution to the problem. Medical ozone has yielded excellent results in intervertebral disc pathology. When it comes to extruded disc herniation, ozone is the only etiological treatment because it stimulates the immune system to absorb the herniated portion of the nucleus pulposus, thus resolving discal extrusion. This work aims to examine the biomolecular mechanisms that lead to intervertebral disc degeneration while highlighting the significance of oxidative stress and chronic inflammation. Considering that ozone is a regulator of oxidative stress and, therefore, of inflammation, we assert that medical ozone could modulate this process and obtain inflammatory stage macrophages (M1) to switch to the repair phase (M2). Consequently, the ozone would be a therapeutic resource that would work on the etiology of the disease as an epigenetic regulator that would help repair the intervertebral space.

Association between intervertebral disc degeneration and Behçet's disease.

Behçet's disease (BD) is a chronic systemic vasculitis with a wide range of clinical findings. It has both autoinflammatory and autoimmune features and manifests with recurrent inflammatory attacks involving the innate immune system. Recently, autoinflammation has started to take place in the pathogenesis of intervertebral disc degeneration. The aim of this study is to evaluate the relationship between intervertebral disc degeneration and BD. We evaluated patients with BD who suffered neck or low back pain in the last 1 year. Eighty four patients underwent musculoskeletal system examination with MRI imaging of the cervical and lumbar vertebrae, and serum levels of IL6, IL8, and TNF-α were determined. The mean age was 47.7 ± 11.5 (range 20-68) years. Cervical and/or lumbar herniation was detected in the MRI imaging of 65 (77.3%) out of 84 patients. The mean IL8 levels of the group with pain and disc herniation and the group with pain and bulging were statistically significantly higher than the other groups (p = 0.007; p = 0.045, respectively). Chronic inflammation in BD may cause disc degeneration and radicular pain to begin and progress earlier in patients.

Establishing a through-puncture model for assessing post-injection leakage in the intervertebral disc.

PURPOSE: Needle injection through the outer annulus fibrosus of the intervertebral disc (IVD) is the most practical approach for delivery of therapeutic agents, which have been shown to potentially leak following needle retraction. The goal of this work was to establish a protocol for quantifying post-injection leakage and test its sensitivity to factors believed to affect needle track geometry. METHODS: A through-puncture defect procedure, followed by controlled injection, was performed on bovine caudal IVDs. Sensitivity to needle size was tested by injection of saline into unconstrained discs with either a 30G, 26G, or 21G hypodermic needle. Sensitivity to axial load was tested by repeated injection via a 26G needle with either no constraint, fixed height, or 10% axial compressive strain. Sensitivity to flexion was tested by applying combined 0.2 MPa compression and 15° of flexion following injection of 5% of disc volume. RESULTS: Needle diameter significantly affected maximum volume prior to leakage, ranging from 34.6 ± 31.9 µL when using 21G to 115.6 ± 23.6 µL when using 30G. While all unloaded discs leaked, axial compression decreased the incidence of leakage events by 50-100% depending on load history. Forward flexion resulted in a 22% incidence of leakage. CONCLUSION: Fluid injected into IVDs is at significant risk of leakage following needle retraction. This risk depends on factors which alter the geometry of the needle track, including needle size, pinching due to axial compression, and stretching as a result of forward flexion.

ProDisc-C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study.

PURPOSE: Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment disease (ASD) at 24-months post-surgery in Asian patients with symptomatic cervical disc disease (SCDD). METHODS: This multicentre, prospective, randomized controlled trial was initiated after ethics committee approval at nine centres (China/Hong Kong/Korea/Singapore/Taiwan). Patients with single-level SCDD involving C3-C7-vertebral segments were randomized (2:1) into: group-A treated with ProDisc-C and group-B with ACDF. Assessments were conducted at baseline, 6-weeks, 3/6/12/18/24-months post-surgery and annually thereafter till 84-months. Primary endpoint was overall success at 24-months, defined as composite of: (1) ≥ 20% improvement in neck disability index (NDI); (2) maintained/improved neurologic parameters; (3) no implant removal/revision/re-operation at index level; and (4) no adverse/severe/life-threatening events. RESULTS: Of 120 patients (80ProDisc-C,40ACDF), 76 and 37 were treated as per protocol (PP). Overall success (PP) was 76.5% in group-A and 81.8% in group-B at 24-months (p = 0.12), indicating no clear non-inferiority of ProDisc-C to ACDF. Secondary outcomes improved for both groups with no significant inter-group differences. Occurrence of ASD was higher in group-B with no significant between-group differences. Range of motion (ROM) was sustained with ProDisc-C but lost with ACDF at 24-months. CONCLUSION: Cervical TDR with ProDisc-C is feasible, safe, and effective for treatment of SCDD in Asians. No clear non-inferiority was demonstrated between ProDisc-C and ACDF. However, patients treated with ProDisc-C demonstrated significant improvement in NDI, neurologic success, pain scores, and 36-item-short-form survey, along with ROM preservation at 24-months. Enrolment difficulties resulted in inability to achieve pre-planned sample size to prove non-inferiority. Future Asian-focused, large-scale studies are needed to establish unbiased efficacy of ProDisc-C to ACDF.

Artificial intelligence in predicting early-onset adjacent segment degeneration following anterior cervical discectomy and fusion.

PURPOSE: Anterior cervical discectomy and fusion (ACDF) is a common surgical treatment for degenerative disease in the cervical spine. However, resultant biomechanical alterations may predispose to early-onset adjacent segment degeneration (EO-ASD), which may become symptomatic and require reoperation. This study aimed to develop and validate a machine learning (ML) model to predict EO-ASD following ACDF. METHODS: Retrospective review of prospectively collected data of patients undergoing ACDF at a quaternary referral medical center was performed. Patients > 18 years of age with > 6 months of follow-up and complete pre- and postoperative X-ray and MRI imaging were included. An ML-based algorithm was developed to predict EO-ASD based on preoperative demographic, clinical, and radiographic parameters, and model performance was evaluated according to discrimination and overall performance. RESULTS: In total, 366 ACDF patients were included (50.8% male, mean age 51.4 ± 11.1 years). Over 18.7 ± 20.9 months of follow-up, 97 (26.5%) patients developed EO-ASD. The model demonstrated good discrimination and overall performance according to precision (EO-ASD: 0.70, non-ASD: 0.88), recall (EO-ASD: 0.73, non-ASD: 0.87), accuracy (0.82), F1-score (0.79), Brier score (0.203), and AUC (0.794), with C4/C5 posterior disc bulge, C4/C5 anterior disc bulge, C6 posterior superior osteophyte, presence of osteophytes, and C6/C7 anterior disc bulge identified as the most important predictive features. CONCLUSIONS: Through an ML approach, the model identified risk factors and predicted development of EO-ASD following ACDF with good discrimination and overall performance. By addressing the shortcomings of traditional statistics, ML techniques can support discovery, clinical decision-making, and precision-based spine care.

The association between Roussouly sagittal alignment type and risk for adjacent segment degeneration following short-segment lumbar interbody fusion: a retrospective cohort study.

BACKGROUND: To date, the influence of Roussouly type on development of adjacent segment degeneration (ASD) after lumber fusion is still not fully explored, and the current study is aimed to evaluate the effect of Roussouly type on development of radiological ASD after single-level lumber fusion, and to compare the Roussouly types and spinopelvic parameters among those with different degenerative patterns of ASDs on sagittal plane. METHODS: A retrospective review of 288 patients underwent L4/5 or L5/S1 single-level posterior interbody fusions between January 2016 and December 2018 with a minimum 2-year follow up was performed. Radiological ASDs were identified and divided into 3 groups according to different degenerative patterns of the cephalad adjacent level on sagittal plane, including the types of retrolisthesis (Group A), anterolisthesis (Group B), and axial disc space narrowing (Group C). Roussouly types and radiological measurements were compared among three groups and potential risk factors for ASD were evaluated. RESULTS: Radiological ASD was found in 59 (20.5%) cases, in which patients with Roussouly type-2 was the most common. While, on subgroup analysis among three ASD groups, Roussouly type-1 occupied the highest proportion in Group A, differ in Group B and Group C, both with Type-2 as the most common. Moreover, Group A had significantly lower pelvic tilt (PT), larger sacral slope (SS), and larger segmental angle (SA) than Group B and Group C, which showed a more anteverted pelvic in Group A. Multivariate regression analysis noted Roussouly type, preoperative PT, and ∆PI-LL as the independent risk factors for radiological ASD. CONCLUSION: Roussouly type was significantly associated with the development of radiological ASD; however, the Roussouly types and spinal pelvic parameters were varied among different sagittal degenerative patterns of ASD, which was important in restoring optimal lumbar sagittal alignments in initial surgery.

Risk factors for adjacent segment disease requiring reoperation after posterior lumbar interbody fusion with screw fixation: focus on paraspinal muscle, facet joint, and disc degeneration.

PURPOSE: Adjacent segment disease (ASD) requiring revision surgery is the most serious complication that can occur in patients undergoing posterior lumbar interbody fusion (PLIF) surgery. This study aimed to determine the risk factors for surgical ASD requiring revision surgery after PLIF with screw fixation surgery. We especially focused on paraspinal muscle, facet joint, and disc degeneration. METHODS: Among the patients who underwent PLIF with screw fixation due to degenerative spinal disease from January 2010 to December 2019, patients who underwent revision surgery for the development of ASD were enrolled. To evaluate the risk factors for surgical ASD, we selected a control group. Each patient in the control group was matched by age, sex, fusion level, number of fused segments, secondary MRI follow-up interval, and follow-up duration with a patient in the surgical ASD group. The radiographic and demographic data were compared between the surgical ASD and control groups. RESULTS: There were statistically significant differences between the two groups in radiological parameters of preoperative facet degeneration, facet effusion, facet angle, and fatty degeneration of the multifidus muscle. Multivariable logistic regression analysis revealed that preoperative facet effusion (odds ratio [OR] 6.48), preoperative facet angle (OR 1.24), and progression of fatty degeneration in the multifidus muscle (OR 1.07) were significant risk factors for surgical ASD. CONCLUSIONS: Preexisting high-grade adjacent facet effusion, sagittally oriented facet joint angle, and progressive fatty degeneration of the multifidus muscle are associated with the development of surgical ASD after PLIF surgery.

Chronology of disc degeneration and facet joint arthritis in lumbar spine is variable - A CT based cross-sectional study.

BACKGROUND: The notion that disc degeneration (DD) always precedes facet joint arthritis (FJA) has held sway for many decades. However, it is not always the case. We hypothesized that DD is not always the first offender studied the prevalence of isolated DD and isolated FJA in the lumbar spine. METHODS: Inter-vertebral discs and bilateral facet joints of lumbar spines of 135 participants were graded. The participants were divided into one of the four categories. 'No degeneration,' 'Isolated disc degeneration without facet joint arthritis,' 'Combined disc degeneration and facet joint arthritis,' and 'Isolated facet joint arthritis without disc degeneration.' Multivariate logistic regression analysis was done to evaluate the predictive factors for spinal degeneration using FJA as a dependent variable while age, sex, BMI, smoking history, and DD as predictor variables. RESULTS: The majority of participants had isolated FJA 64 (47.4%). Combined DD and FJA were noted in 32 (23.7%), isolated DD in 8 (5.9%), while 31(23%) had no degeneration. Only age was found to be significantly contributing to the prediction model in multivariate analysis. CONCLUSION: Our study shows that spinal degeneration may begin either in the disc or in the facet joints depending upon the aetiological factors. It is a vicious circle that may be entered at any point, FJA or DD.

Relationship between degree of separation of endplate cartilage and severity of intervertebral disc herniation.

Degeneration of intervertebral disc and fissures in the anulus was caused by compression and distraction, which lead to nucleus pulposus herniation. However, controversy remains regarding the exact mechanism behind disc herniation. The aim of this study is to analyze histologically the differences between the three types of disc herniations in an attempt to infer the underlying mechanism. Disc samples extracted from 49 patients who underwent discectomy of the lumbar region were studied by histological analysis. The severity of disc herniation was classified as bulging, protrusion, extrusion, or sequestration based on preoperative magnetic resonance imaging measurements. For comparative analysis of sequestration characteristics, 49 patients were classified into either the sequestration or the non-sequestration group (i.e., protrusion and extrusion) according to disc herniation type. Forty of the 49 patients had cartilage present in their disc samples upon histological analysis. The endplate cartilage-containing samples included two of four (50%) protruded disc patients, 22 of 29 (75.9%) extruded disc patients, and 16 of 16 (100%) sequestrated disc patients and had statistical significance (p = 0.019). There were no significant differences in age, sex, body mass index, length of hospital stays, injection history, surgical methods, and Visual Analog Scale between the sequestration and non-sequestration group (all p > 0.05). Separation of endplate cartilage increased with the severity of disc herniation. Therefore, the mechanism of disc herniation should consider the connection with endplate cartilage as an initiating link in the mechanical failure of intervertebral discs.

Recent Advances in Managing Spinal Intervertebral Discs Degeneration.

Low back pain (LBP) represents a frequent and debilitating condition affecting a large part of the global population and posing a worldwide health and economic burden. The major cause of LBP is intervertebral disc degeneration (IDD), a complex disease that can further aggravate and give rise to severe spine problems. As most of the current treatments for IDD either only alleviate the associated symptoms or expose patients to the risk of intraoperative and postoperative complications, there is a pressing need to develop better therapeutic strategies. In this respect, the present paper first describes the pathogenesis and etiology of IDD to set the framework for what has to be combated to restore the normal state of intervertebral discs (IVDs), then further elaborates on the recent advances in managing IDD. Specifically, there are reviewed bioactive compounds and growth factors that have shown promising potential against underlying factors of IDD, cell-based therapies for IVD regeneration, biomimetic artificial IVDs, and several other emerging IDD therapeutic options (e.g., exosomes, RNA approaches, and artificial intelligence).

A novel rat model of vertebral inflammation-induced intervertebral disc degeneration mediated by activating cGAS/STING molecular pathway.

In this study, we describe a new rat model of vertebral inflammation-induced caudal intervertebral disc degeneration (VI-IVDD), in which IVD structure was not damaged and controllable segment and speed degeneration was achieved. VI-IVDD model was obtained by placing lipopolysaccharide (LPS) in the caudal vertebral bodies of rats. Rat experimental groups were set as follows: normal control group, group with a hole drilled in the middle of vertebral body and not filled with LPS (Blank group), group with a hole drilled in the middle of vertebral body and filled with LPS (Mid group), and group with hole drilled in the vertebral body in proximity of IVD and filled with LPS (NIVD group). Radiological results of VI-IVDD rats showed a significant reduction in the intervertebral space height and decrease in MRI T2 signal intensity. Histological stainings also revealed that the more the nucleus pulposus and endplate degenerated, the more the annulus fibrosus structure appeared disorganized. Immunohistochemistry analysis demonstrated that the expression of Aggrecan and collagen-II decreased, whereas that of MMP-3 increased in Mid and NIVD groups. Abundant local production of pro-inflammatory cytokines was detected together with increased infiltration of M1 macrophages in Mid and NIVD groups. Apoptosis ratio remarkably enhanced in Mid and NIVD groups. Interestingly, we found a strong activation of the cyclic GMP-AMP synthase /stimulator of interferon gene signalling pathway, which is strictly related to inflammatory and degenerative diseases. In this study, we generated a new, reliable and reproducible IVDD rat model, in which controllable segment and speed degeneration was achieved.

CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro.

BACKGROUND: Nucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity. METHOD: In Vitro, H2O2 was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model. RESULT: In vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (H2O2) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3. CONCLUSIONS: The experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by H2O2 could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.

Roles of NLRP3 inflammasome in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain and one of the most common health problems in the world. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, as a pattern recognition receptor, has been shown to be associated with the pathological processes of many diseases in recent years. With the exploration of the mechanism of IVDD, recent studies have shown that activation of the NLRP3 inflammasome is associated with intervertebral disc (IVD) inflammation, pyroptosis, extracellular matrix degradation and apoptosis of IVD cells. In this review, we summarize the structural characteristics of NLRP3 inflammasome and the activation signalling mechanisms. We also describe the role of the NLRP3 inflammasome in the pathological process of IVDD and the application of the targeting the NLRP3 inflammasome in IVDD treatment.

MicroRNA-140-3p alleviates intervertebral disc degeneration via KLF5/N-cadherin/MDM2/Slug axis.

MicroRNAs (miRNAs) are associated with healing or deteriorating degenerated intervertebral disc (IVD) tissues in spinal cord diseases, including intervertebral disc degeneration (IDD). IDD represents a chronic process of extracellular matrix destruction, but the relevant molecular mechanisms implicated in the regenerative effects of miRNAs are unclear. Here, we investigated the regenerative effects of microRNA-140 (miR-140-3p) in an IDD model induced by annulus needle puncture. Bioinformatics analysis was conducted to identify regulatory factors (KLF5/N-cadherin/MDM2/Slug) linked to miR-140-3p effects in IDD. Mesenchymal stem cells (MSCs) were extracted from degenerated IVD nucleus pulposus (NP), and the expression of miR-140-3p/KLF5/N-cadherin/MDM2/Slug was manipulated to explore their effects on cell proliferation, migration, apoptosis and differentiation. The results showed that miR-140-3p was under-expressed in the degenerated IVD NP, whereas its overexpression alleviated IDD. Mechanistic studies suggested that miR-140-3p targeted KLF5 expression, and high KLF5 expression impeded the migration and differentiation of MSCs. In degenerated IVD NP-derived MSCs, MiR-140-3p-mediated KLF5 downregulation simultaneously elevated N-cadherin expression and transcriptionally inhibited MDM2, thus upregulating Slug expression. The experimental data indicated that miR-140-3p enhanced the proliferation, migration and differentiation of degenerated IVD NP-derived MSCs and repressed their apoptosis. The in vivo validation experiment also demonstrated that miR-140-3p inhibited IDD by modulating the KLF5/N-cadherin/MDM2/Slug axis. Collectively, our results uncovered the regenerative role of miR-140-3p in IDD via regulation of the KLF5/N-cadherin/MDM2/Slug axis, which could be a potential therapeutic target for IDD.Abbreviations: miR-140-3p: microRNA-140-3p; IDD: intervertebral disc degeneration; MSCs: Mesenchymal stem cells; IVD: intervertebral disc; MSCs: mesenchymal stem cells; KLF5: Kruppel-like factor 5; MDM2: mouse double minute 2; NC: negative control; DHI: disc height index.

Acute effects of varying squat depths on lumbar intervertebral disks during high-load barbell back squat exercise.

We aimed to evaluate the acute physiological effects of high-load barbell back squat exercise on each lumbar intervertebral disk with varying squat depths. Thirteen subjects (age, 23.3 ± 3.5 years) performed parallel and half-squat exercises (80% of one repetition maximum, eight repetitions, five sets) using a Smith machine. Sagittal magnetic resonance diffusion-weighted and spin-echo images of lumbar intervertebral disks were obtained by using a 1.5-Tesla MR system before and after each squat exercise; apparent diffusion coefficient (ADC; an index of water movement) and T2 relaxation time (an index of water content level) of the nucleus pulposus were calculated at all lumbar intervertebral disks. Additionally, we measured the angles of lumbar lordosis and anterior pelvic tilt at the bottom position of each squat using a three-dimensional motion-capture system. The nucleus pulposus of L4/5 (-5.0%, P < .01) and L5/S1 (-6.6%, P < .01) intervertebral disks showed decreased ADC values after parallel squat exercise. Moreover, post-exercise ADC value in parallel squat exercise was lower than that in half-squat exercise at L5/S1 intervertebral disk (P < .05). In contrast, the nucleus pulposus of all lumbar intervertebral disks had no significant T2 change before and after both squat exercises. The angles of lumbar lordosis (P < .01) and anterior pelvic tilt (P < .01) were smaller in parallel squat than in half-squat. Lower lumbar intervertebral disks are subject to greater mechanical stress during high-load parallel back squat exercise, which may result from smaller lumbar lordosis and anterior pelvic tilt angles at the bottom position during parallel squat.

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1-5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

Can formetric 4D measurements predict the development of adjacent segment degeneration after single-segment PLIF?: Relative rotation angle as a sensitive predictor.

BACKGROUND: Adjacent segment degeneration (ASD) is a major issue after posterior lumbar interbody fusion (PLIF). The postoperative dynamic change of adjacent segments remains unknown. Hence, this study using the formetric 4D system (DIERS, International GmbH of Schlangenbad, Germany) to determine the impact of PLIF on ASD, and to compare the effectiveness with traditional radiography for the predication of ASD. METHODS: Eighty-five consecutive patients who underwent PLIF of a single-segment were included. The formetric 4D system was used to calculate the relative rotation angle between the fusion segment and the upper and lower adjacent vertebrae before and at 6, 12 and 24 months after surgery. The range of motion (ROM) and disc height (DH) of adjacent segments were measured using radiography before surgery and 24 months postoperatively. At the final follow-up, the visual analogue scale (VAS) and Oswestry disability index were used to evaluate the surgical outcome. The patients were divided into two groups according to the occurrence of radiographic ASD: the ASD group with progression of degeneration and the N-ASD group without progression of degeneration. RESULTS: The index fusion segments included L2-3 to L5-S1. Preoperatively, the relative rotation angles formed by the fusion segment with the upper and lower adjacent vertebrae were 5.1° ± 2.2° and 3.3° ± 2.0°, respectively, and both angles increased significantly at all time points after surgery (p < 0.05). The angles changed most significantly during L2-3 fusion. Radiographic ASD developed in 13 of 85 patients (15.3%) at 24 months. And the relative rotation angle with the upper adjacent vertebra was larger in the ASD group than in the N-ASD group (p < 0.05). CONCLUSION: The relative rotation angle with adjacent vertebra increased significantly after lumbar fusion surgery. It may be a more sensitive predictor than the flexion-extension ROM and DH for the development of radiographic ASD.