Changes In Intervertebral Discs Research Articles

Impact of bilateral facet joint violation on radiographic degeneration of superior adjacent segments and clinical outcomes.

Facet joint violation (FJV) is associated with postoperative low-back pain and is a confirmed risk factor for adjacent-segment degeneration, a long-term complication of lumbar fusion surgery. The authors' knowledge of its mechanisms comes from in vitro biomechanical research only; there is a lack of radiographic evidence of the effects of violation on the superior adjacent-segment facet joint, intervertebral disc, and other local radiographic parameters. Furthermore, any differences between unilateral and bilateral violation remain relatively unclear. The authors therefore aimed to explore the effects of nonviolation and unilateral and bilateral violation on radiographic degeneration of the facet joint and intervertebral disc at the fusion and superior adjacent segment. Patient-reported clinical outcomes were compared at the 2-year follow-up. The authors retrospectively analyzed data from 148 patients with lumbar degenerative diseases who underwent single-segment minimally invasive transforaminal lumbar interbody fusion between 2016 and 2020. FJV and facet joint degeneration were evaluated and graded using Shah's method and Pathria's standard, respectively. Radiographic parameters, including disc height and intervertebral Cobb angle at the fusion and superior adjacent segment, were measured. Clinical outcomes were evaluated using visual analog scale (VAS) and Japanese Orthopaedic Association scores. Preoperative data were comparable among the 3 groups (nonviolation, unilateral violation, and bilateral violation) (p > 0.05). Patient-reported clinical outcomes were followed up for at least 2 years (average duration 28.17 ± 6.17 months). At the last follow-up, facet joint degeneration grades were sequentially increased in the nonviolation, unilateral violation, and bilateral violation groups (p = 0.006). The unilateral (2.45 ± 2.17 mm) and bilateral (2.70 ± 1.94 mm) violation groups had more severe losses of disc height in the superior adjacent segment than did the nonviolation group (1.31 ± 2.01 mm). The VAS low-back pain and Japanese Orthopaedic Association scores in the bilateral (2.57 ± 1.44 and 19.83 ± 2.84, respectively) and unilateral (2.26 ± 0.79 and 20.43 ± 3.85, respectively) violation groups were significantly worse than in the nonviolation group (1.69 ± 1.12 and 21.80 ± 3.36, respectively) (p < 0.05). By contrast, there were no significant between-group differences in disc height, intervertebral Cobb angle in the fusion segment, or VAS leg pain scores (p > 0.05). FJV was associated with postoperative low-back pain and worse functional outcomes. It also aggravated facet joint and intervertebral disc changes in the superior adjacent segment, especially when bilateral violation occurred; this may be part of the mechanisms of adjacent-segment degeneration.

Biochemical changes in lumbar facet joint and disc degeneration by T2* mapping

BackgroundTo investigate the biochemical changes in lumbar facet joint (LFJ) and intervertebral disc (IVD) with different degenerative grade by T2* mapping.MethodsSixty-eight patients with low back pain (study group) and 20 volunteers (control group) underwent standard MRI protocols and axial T2* mapping. Morphological evaluation of LFJ and IVD were performed on T2-weighted imaging according to Weishaupt and Pfirrmann grading system, respectively. T2* values of LFJ and of AF (anterior annulus fibrosus), NP (nucleus pulposus), and PF (posterior annulus fibrosus) in IVD were measured. Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare T2* values of subjects with different degenerative grade.ResultsThe mean T2* value of grade 0 LFJ (21.68[17.77,26.13]) was higher than those of grade I (18.42[15.68,21.8], p < 0.001), grade II (18.98[15.56,22.76], p = 0.011) and grade III (18.38[16.05,25.07], p = 0.575) LFJ in study group, and a moderate correlation was observed between T2* value and LFJ grade (rho=-0.304, p < 0.001) in control group. In the analysis of IVD, a moderate correlation was observed between AF T2* value and IVD grade (rho=-0.323, p < 0.001), and between NP T2* value and IVD grade (rho=-0.328, p < 0.001), while no significant difference was observed between the T2* values of PF in IVD of different grade in study group.ConclusionsDownward trend of T2* values can be found in LFJ, AF and NP as the degenerative grade rised. But in elderly patients with low back pain, no change trend was found in LFJ due to increased fluid accumulation in the joint space.

A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc.

Interactions between notochord and sclerotome are required for normal embryonic spine patterning, but whether the postnatal derivatives of these tissues also require interactions for postnatal intervertebral disc (IVD) growth and maintenance is less established. We report here the comparative analysis of four conditional knockout mice deficient for TonEBP, a transcription factor known to allow cells to adapt to changes in extracellular osmotic pressure, in specific compartments of the IVD. We show that TonEBP deletion in nucleus pulposus (NP) cells does not affect their survival or aggrecan expression, but promoted cell proliferation in the NP and in adjacent vertebral growth plates (GPs). In cartilage end plates/GPs, TonEBP deletion induced cell death, but also structural alterations in the adjacent NP cells and vertebral bodies. Embryonic or postnatal TonEBP loss generated similar IVD changes. In addition to demonstrating the requirement of TonEBP in the different compartments of the IVD, this comparative analysis uncovers the in vivo interdependency of the different IVD compartments during the growth of the postnatal IVD-vertebral units.

Efficacy of wet cupping in the pain management of cervical spondylosis – A randomized, controlled, open -label, parallel-group clinical trial

Background and objectiveCervical spondylosis is a chronic degenerative process of the cervical spine characterized by pain in neck, degenerative changes in intervertebral disc and osteophyte formation. Cervical spondylosis is translated as Wajaʻ ur Raqaba, a type of joint pain. The present study was aimed to evaluate the effect of wet cupping in the pain management of cervical spondylosis. MethodsThis Open, randomized, controlled, clinical study was conducted on 44 patients. Subjects in the test group (n = 22) received a series of three-staged wet cupping treatment, performed on 0, 7th and 14th day. Subjects in the control group (n = 22) received 12 sittings of Transcutaneous Electrical Nerve Stimulation (TENS): 6 sittings per week for two weeks. The objective findings of treatment were assessed with the help of VAS, Neck Disability Index (NDI) and Cervical range of motion. ResultsIntra group comparison in test group from baseline to 21st day were found highly significant (p < 0.001) in terms of VAS, NDI, Flexion, Extension and Left rotation score. While in Right rotation, Left rotation and Left lateral flexion score were found moderately significant (p < 0.01). Statistically significant difference was observed between two groups at 21st day in VAS scale, NDI, and Cervical range of motion score (p < 0.001). Interpretation and conclusionḤijāma Bish Sharṭ was found better in the management of pain due to cervical spondylosis than TENS. It can be concluded that Ḥijāma Bish Sharṭ may a better option for the pain management of cervical spondylosis. Clinical trial registrationThe trial was registered on clinical trial registry website (www.ctri.nic.in) bearing a CTRI Number, CTRI/2020/03/024,249.

Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway.

Intervertebral disc (IVD) degeneration (IDD) is a worldwide spinal degenerative disease. Low back pain (LBP) is frequently caused by a variety of conditions brought on by IDD, including IVD herniation and spinal stenosis, etc. These conditions bring substantial physical and psychological pressure and economic burden to patients. IDD is closely tied with the structural or functional changes of the IVD tissue and can be caused by various complex factors like senescence, genetics, and trauma. The IVD dysfunction and structural changes can result from extracellular matrix (ECM) degradation, differentiation, inflammation, oxidative stress, mechanical stress, and senescence of IVD cells. At present, the treatment of IDD is basically to alleviate the symptoms, but not from the pathophysiological changes of IVD. Interestingly, the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in many processes of IDD, including inflammation, ECM degradation, apoptosis, senescence, proliferation, oxidative stress, and autophagy. These activities in degenerated IVD tissue are closely relevant to the development trend of IDD. Hence, the p38 MAPK signaling pathway may be a fitting curative target for IDD. In order to better understand the pathophysiological alterations of the intervertebral disc tissue during IDD and offer potential paths for targeted treatments for intervertebral disc degeneration, this article reviews the purpose of the p38 MAPK signaling pathway in IDD.

The relationship between structural changes in paraspinal muscles and intervertebral disc and facet joint degeneration in the lumbar spine of rats

BackgroundDegenerative spine disease is one of the largest causes of disability worldwide and has a multifactorial aetiology. Determining the leading causes of this multifactorial disease could help create new treatment approaches.PurposeStudy the impact of degenerative changes in the paraspinal muscles caused by local (prolonged compression) or systemic (high-fat diet) factors on the structure of the intervertebral discs (IVDs) and facet joints of the lumbar spine in rats.MethodsThe study was conducted using two animal models to create degenerative changes in the paraspinal muscles of 10 white laboratory rats for 90 days and five control rats: 1) high-fat diet model (model 1) involved keeping the rats on a high calorie diet; 2) compression model (model 2) involved binding the paraspinal muscles from L2 to S1 using non-absorbable sutures. Histological analysis for the facet joints and IVDs of rats (at the L1–L4 level) with semi-quantitative analysis of the structure conducted used by degeneration grading system for IVDs and cartilage degeneration score (OARSI) for facet joint.ResultsIn both models, 90 days after the experiment, the degenerative changes observed in the rats’ IVDs were more severe in the annulus fibrosus than in the nucleus pulposus. The height of the IVD in model 1 did not differ from the control group, but in the model 2 was 1.3 times greater (p < 0.001) compared with control. Degenerative changes in the IVD were scored out 5.3 ± 1.7 in model 1 and 5.32 ± 2.1 in model 2 of a possible 16. The height of the articular cartilage of the facet joints was smaller by 1.5 times (p < 0.001) and 1.4 times (p < 0.001) in model 1 and model 2, respectively, compared to the control. Degenerative changes of facet joint were scored out 3.7 ± 0.6 in model 1 and 3.8 ± 0.6 in model 2 of five points according to the cartilage degeneration score.ConclusionsIt was determined that rats who had structural changes in the lumbar paraspinal muscles as a result of being kept on a high-fat diet or subjected to prolonged compression for 90 days, showed degenerative changes in intervertebral discs and osteoarthritis in facet joints of lumbar spine.

Impact of Running Exercise on Intervertebral Disc: A Systematic Review.

Running is one of the most popular sports worldwide. However, controversies exist regarding how running affects runner's intervertebral discs (IVD). The purpose of this study was to systematically review studies that evaluated IVD morphology or composition changes in response to running exercise, to determine the impact of running exercise on IVD. A systematic literature search was performed for 4 major databases: PubMed, Cochrane, Embase, and Web of Science. Inclusion criteria were as follows: (1) healthy people without known IVD disease or major complications such as tuberculosis (IVD degeneration or low back pain are considered as minor complications); (2) subjects performed 1-time or regular running exercises; (3) pre and post comparison of runners or comparison between runners and healthy control subjects; (4) direct or indirect IVD morphology or composition measured; (5) IVD assessed before and after either acute or chronic running exercise, or compared cross-sectionally between runners and controls. Exclusion criteria were as follows: (1) reviews, editorials, letters or abstracts only; (2) animal studies; (3) subjects performed exercise other than running. Systematic review. Level 3. The extracted data included study design and primary outcomes of the included studies. The Newcastle-Ottawa scale (NOS) was used to evaluate study quality and risk of bias. A total of 13 studies with 632 participants were included in the final analysis; 4 studies measured IVD changes using stature or spinal height, and the other 9 measured IVD changes using magnetic resonance imaging; 6 studies found that running acutely and negatively impacts IVD; 3 out of 5 cross-sectional studies found that IVD parameters are better for runners than controls; 1 longitudinal study found no significant difference in IVD before and after training for marathon in runners; 1 longitudinal study found no significant difference in changes of IVD between runners and controls after 15 years of follow-up. Negative changes in IVD exist for a short period of time after running, which may be due to the temporary compression pushing water content out of the disc. Cross-sectional studies suggest that long-term running exerts a mild positive effect on IVD; however, this inference has not been confirmed by high-quality longitudinal studies.

Coexistence of Vertebral and Intervertebral Disc Changes in Low Back Pain Patients—In Depth Characterization with Same Day MRI and CT Discography

The aim of this study was to investigate to what extent annular fissures, vertebral and endplate changes, and Modic changes (MCs), coexist in low back pain (LBP) patients by using multiple imaging modalities. Sixty-two LBP patients (mean age 45 years, range 24–63, 53% men) were examined with same-day CT-discography and MRI. Intervertebral discs punctured for discography (n = 204) were evaluated on MRI [Pfirrmann grade, High-Intensity Zone (HIZ)] and on CT-discograms [Modified Dallas Discogram Score (DDS)]. DDS≥ 1, i.e., disc fissures involving the outer annulus were further digitomized into delimitable fissuring (&lt;50% of annulus affected) or non-delimitable annular fissuring. Using both MRI and CT, adjacent vertebrae and endplates were assessed for MC, vertebral sclerosis, and a modified endplate defect score (EPS). In 194 discs the contrast agent was adequately injected during discography, of which 160 (83%) displayed outer annular fissures, with 91 (47%) of the latter being delimitable fissures. Most discs with delimitable fissures were moderately degenerated; 68% Pfirrmann grade ≤3, 71% EPS ≤ 2, and 12% displayed MC. The majority (76%) of MCs were associated with advanced adjacent disc degeneration; 84% Pfirrmann grade ≥4, 76% with non-delimitable annular fissuring, 59% EPS≥ 4, and 34% EPS of 3. A total 95 HIZ (47%) were found, of which 54 had delimitable fissuring, while the remainder displayed non-delimitable fissuring. Vertebral sclerosis was commonly observed (26%), both with MCs (73%) and without MCs (27%), and not specifically linked to MC type 3. A total of 97% of segments with vertebral sclerosis displayed outer annular fissures. These findings were significant (0.046 &gt; p &gt; 0.0001), except between HIZ and adjacent sclerosis (p = 0.303). To conclude, the present study confirmed a close interplay between the disc and adjacent vertebra and endplates. The fact that a majority of discs with delimitable annular fissures did not coexist with pronounced endplate changes and/or MCs, however, supports the theory that disc fissuring is an early event in the degenerative cascade. This was further supported by the fact that MCs were strongly linked to extensive disc fissuring and to advanced endplate damage. Further, vertebral sclerosis was common also in vertebra without MCs and strongly associated to annular fissuring, indicating that sclerosis is a previously underestimated feature of a general degenerative process.

A novel rat model of annulus fibrosus injury for intervertebral disc degeneration

BACKGROUND CONTEXTIn clinical practice, acute trauma and chronic degeneration of the annulus fibrosus (AF) can promote further degeneration of the intervertebral disc (IVD). Therefore, it is critical to understand the AF repair process and its consequences on IVD. However, the lack of cost-effective and reproducible in vivo animal models of AF injury has limited research development in this field. PURPOSESThe purpose of this study was to establish and evaluate the utility of a novel animal model for full-thickness AF injury. Three foci were proposed: (1) whether this new modeling method can cause full-layer AF damage; (2) the repair processes and pathological changes in the damaged area after AF injury, and (3) the morphological and histological changes in the IVD are after AF injury. STUDY DESIGN/SETTINGIn vivo rat AF injury model with characterization of AF damage repair, IVD degeneration. METHODSA total of 72,300 g male rats were randomly assigned to one of the two groups: experimental or sham. Annulus fibrosus was separated layer by layer under the microscope with a #11 blade up to the AF- nucleus pulpous (NP) junction. The repair process of the horizontal AF and morphological changes in the sagittal IVD were evaluated with HE staining. Sirius red staining under polarized light. Immunofluorescence was conducted to analyze changes in the expression of COL1 and COL3 in the AF injury area and 8-OHdg, IL-6, MMP13, FSP1, and ACAN in the IVD. The disc height and structural changes after AF injury were measured using X-ray and contrast-enhanced micro-CT. Additionally, the resistance of the AF to stretching was analyzed using three-point bending. RESULTSAnnulus fibrosus-nucleus pulpous border was identified to stably induce the full-thickness AF injury without causing immediate NP injury. The AF repair process after injury was slow and expressed inflammation factors continuously, with abundant amounts of type III collagen appearing in the inner part of the AF. The scar at the AF lesion had decreased resistance to small molecule penetration and weakened tensile strength. Full-thickness AF injury induced disc degeneration with loss of disc height, progressive unilateral vertebral collapse, and ossification of the subchondral bone. Inflammatory-induced degeneration and extracellular matrix catabolism gradually appeared in the NP and cartilage endplate (CEP). CONCLUSIONSWe established a low-cost and reproducible small animal model of AF injury which accurately replicated the pathological state of the limited AF self-repair ability and demonstrated that injury to the AF alone could cause further degeneration of the IVD. CLINICAL RELEVANCEThis in vivo rat model can be used to study the repair process of the AF defect and pathological changes in the gradual degeneration of IVD after AF damage. In addition, the model provides an experimental platform for in vivo experimental research of potential clinical therapeutics.

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects. This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein. We exploited a rat needle model to investigate digoxin's role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin. Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells. These findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.

Linking histopathological changes in intervertebral disc with lumbar muscles strength.

Low back pain (LBP) is a painful condition affecting 80% of word population at some point in their life. Lumbar intervertebral disc degeneration and reduced muscle force is one the major cause of LBP. Sixty-two patients with LBP undergoing discectomy were recruited after receiving consent. Lumbar muscles strength and VAS (visual analogue scale) for lumbar pain were checked, MRI scan were analysed. Histological degenerative changes were analysed. The study revealed histological degeneration at intervertebral disc has direct effect on increase in pain at lumbar region, decrease in strength of lumbar flexor and extensors muscles and degenerative changes seen on MRI scan.

MR imaging of thoracic annular fissures

ObjectiveAnnular fissures are common findings on MR studies of the lumbar spine but have not been specifically examined in the thoracic spine. We sought to review the prevalence and stability of MRI imaging features of thoracic annular fissures and the association of thoracic AFs with intervertebral degenerative disk changes. Materials and methodsWe surveyed 10 years of MRI studies in which patients had one or more repeated examinations of the thoracic spine. For every annular fissure, we recorded its imaging features on all pulse sequences and the evolution of those imaging findings across all time periods. ResultsWe reviewed 210 patients and discovered that 66 (31.4%) had at least one thoracic annular fissure. The presence of annular fissures was positively correlated with older age and male gender. The initial annular fissure was always hyperintense on T2WI and annular fissures remained hyperintense on T2WI over time in all cases but showed less hyperintensity in 23.9% (n = 39/163) and more hyperintensity in 4.9% (n = 8/163). The rate of concomitant disk bulges was 85.8% (n = 140/163). Of the 71 annular fissures in which gadolinium-enhanced studies were performed, 20 (28.1%) showed enhancement and 14/20 (70%) annular fissures showed persistent enhancement over time (mean follow-up = 39.6 ± 44.1 months). ConclusionThoracic annular fissures rarely resolve, remain hyperintense on T2WI, and, if they enhance, that enhancement generally persists.

Anatomical Changes of Intervertebral Disc with Age: MRI Study Using Quantitative Measure

Anatomical Changes of Intervertebral Disc with Age: MRI Study Using Quantitative Measure

Effect of acupotomy intervention on the expressions of proteoglycans in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration

To observe the effect of acupotomy intervention on the expressions of biglycan(BGN), decorin(DCN) and Caspase-3 in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration (LIDD), so as to explore its possible mechanism in relieving LIDD. Thirty male Japanese white rabbits were randomly divided into normal, model and acupotomy groups, with 10 rabbits in each group. The LIDD model was established by axial compression method, and magnetic resonance imaging (MRI) was used to judge whether the model was successful or not. After modeling, the acupotomy was applied to lumbar (L)4-L5 spinous process space and bilateral transverse processes for loosening, twice a week for 4 weeks. The structural changes of L4-L5 intervertebral disc were observed by MRI. The morphological changes of lumbar spine were observed by HE staining. The expression of Caspase-3 in nucleus pulposus was observed by immunohistochemistry, and the protein expressions of DCN and BGN in intervertebral disc were detected by Western blot, separatively. After mode-ling, the rabbits showed slow movement, stiff back muscles with cords or nodules, the fibrous ring structure of lumbar intervertebral disc was disordered, the number of nucleus pulposus cells was reduced, and the signal intensity of L4-L5 intervertebral disc was decreased in the model group relevant to the normal group. At the same time, the expression of Caspase-3 in nucleus pulposus was increased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were decreased significantly (P<0.05). After acupotomy treatment, the modeling induced slow movement, stiff back muscles and disordered structure of lumbar intervertebral disc were significantly improved. The number of nucleus pulposus cells was increased, the signal intensity of L4-L5 intervertebral disc was enhanced, the expression of Caspase-3 in nucleus pulposus was decreased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were increased significantly (P<0.05) compared with the model group. Acupotomy intervention can inhibit cell apoptosis, reduce the degradation of extracellular matrix in nucleus pulposus of intervertebral disc, and restore the normal force balance and dynamic balance of lumbar spine, which may be one of its mechanisms underlying improving LIDD.

An in vivo model of ligamentum flavum hypertrophy from early-stage inflammation to fibrosis.

Multi-joint disease pathologies in the lumbar spine, including ligamentum flavum (LF) hypertrophy and intervertebral disc (IVD) bulging or herniation contribute to lumbar spinal stenosis (LSS), a highly prevalent condition characterized by symptomatic narrowing of the spinal canal. Clinical hypertrophic LF is characterized by a loss of elastic fibers and increase in collagen fibers, resulting in fibrotic thickening and scar formation. In this study, we created an injury model to test the hypothesis that LF needle scrape injury in the rat will result in hypertrophy of the LF characterized by altered tissue geometry, matrix organization, composition and inflammation. An initial pilot study was conducted to evaluate effect of needle size. Results indicate that LF needle scrape injury using a 22G needle produced upregulation of the pro-inflammatory cytokine Il6 at 1 week post injury, and increased expression of Ctgf and Tgfb1 at 8 weeks post injury, along with persistent presence of infiltrating macrophages at 1, 3, and 8 weeks post injury. LF integrity was also altered, evidenced by increases in LF tissue thickness and loss of elastic tissue by 8 weeks post injury. Persistent LF injury also produced multi-joint effects in the lumbar IVD, including disc height loss at the injury and adjacent to injury level, with degenerative IVD changes observed in the adjacent level. These results demonstrate that LF scrape injury in the rat produces structural and molecular features of LF hypertrophy and IVD height and histological changes, dependent on level. This model may be useful for testing of therapeutic interventions for treatment of LSS and IVD degeneration associated with LF hypertrophy.

Radiological outcomes of PEEK rods in patients with lumbar degenerative diseases: A minimum 5-year follow-up.

To determine the long-term radiological outcomes of PEEK rods in patients with lumbar degenerative diseases. Radiological outcomes of cohort cases with lumbar degenerative diseases following PEEK rods were retrospectively studied. Disc height index (DHI) and range of motion (ROM) were measured by x-rays. The CT scans and reconstruction were used to determine screw breakage, rods fracture, screw loosening and intervertebral bony fusion status. The MRI scans were used to evaluate the changes of intervertebral discs at the non-fusion segments and adjacent segments in terms of Pfirrmann Classification. A total of 40 patients completed the mean of 74.8 ± 9.6 months follow-up, with 32 patients undergoing hybrid surgery and 8 patients undergoing non-fusion surgery. The mean DHI changed from preoperative 0.34 to 0.36 at the final follow-up and the ROM declined from 8.8° preoperatively to 3.2° at the final visit, however, both had no statistical differences. Of the 40 levels underwent non-fusion procedure, 9 levels showed disc rehydration with 7 patients from Grade 4 to Grade 3 and 2 patients from Grade 3 to Grade 2. The other 30 cases did not show distinctive change. No screw loosening or rods breakage were detected during the follow-up periods. PEEK rods have obvious protective effects on degenerated intervertebral disc of non-fusion segments and the incidence of complications related to internal fixation is low. PEEK rods pedicle screw system is safe and effective in the treatment of lumbar degenerative diseases.

FOXO3-Activated circFGFBP1 Inhibits Extracellular Matrix Degradation and Nucleus Pulposus Cell Death via miR-9-5p/BMP2 Axis in Intervertebral Disc Degeneration In Vivo and In Vitro

(1) Background: intervertebral disc degeneration (IVDD) defined as the degenerative changes in intervertebral disc is characterized by extracellular matrix (ECM) degradation and death in nucleus pulposus (NP) cells. (2) Methods: The model of IVDD was established in male Sprague Dawley rats using a puncture of a 21-gauge needle at the endplates located in the L4/5 intervertebral disc. Primary NP cells were stimulated by 10 ng/mL IL-1β for 24 h to mimic IVDD impairment in vitro. (3) Results: circFGFBP1 was downregulated in the IVDD samples. circFGFBP1 upregulation inhibited apoptosis and extracellular matrix (ECM) degradation and promoted proliferation in IL-1β-stimulated NP cells. Additionally, circFGFBP1 upregulation mitigated the loss of NP tissue and the destruction of the intervertebral disc structure in vivo during IVDD. FOXO3 could bind to the circFGFBP1 promoter to enhance its expression. circFGFBP1 upregulated BMP2 expression in NP via sponging miR-9-5p. FOXO3 enhanced the protection of circFGFBP1 in IL-1β-stimulated NP cells, whereas a miR-9-5p increase partly reversed the protection. miR-9-5p downregulation contributed to the survival of IL-1β-stimulated NP cells, which was partially reversed by BMP2 silence. (4) Conclusions: FOXO3 could activate the transcription of circFGFBP1 via binding to its promoter, which resulted in the enhancement of BMP2 via sponging miR-9-5p and then inhibited apoptosis and ECM degradation in NP cells during IVDD.

A systematic morphology study on the effect of high glucose on intervertebral disc endplate degeneration in mice

To explore the relationship between diabetes and intervertebral disc degeneration in mice and the associated underlying mechanism. Four-week-old male Kunming mice were used to model diabetes using a high-fat diet combined with streptozotocin injection. After 6 months, morphological and pathological changes in L4-L6 intervertebral discs were detected by magnetic resonance imaging, micro-CT and histological staining. Immunostaining of CD31, F4/80 and CD16/32 receptors was used to detect vascular invasion and inflammatory infiltration in endplates; the exact changes were then explored by the transmission electron microscopy. The nucleus pulposus of the control and the diabetic group had a clear boundary and regular shape without collapse, while endplate calcification and chondrocyte abnormality in the diabetic group were more obvious. Immunofluorescence confirmed that compared to control, expression levels of CD31 (vascular endothelial marker) and F4/80 (monocyte/macrophage marker) in the diabetic group were significantly increased (P < 0.05), with an elevated number of F4/80 (+)/CD16/32 (+) cells (P < 0.05). The morphology of endplates was observed by transmission electron microscopy, which showed monocytes/macrophage accumulation in the endplate of the diabetic group, accompanied by increased vascular density, collagen fiber distortion and chondrocyte abnormality. In a conclusion, diabetes promotes endplate degeneration with vascular invasion, monocyte/macrophage infiltration and inflammation in mice.

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics.

Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti-oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain-relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration.

A methodology to evaluate different histological preparations of soft tissues: Intervertebral disc tissues study.

A tissue preparation method will inevitably alter the tissue content. This study aims to evaluate how different common sample preparation methods will affect the tissue morphology, biomechanical properties, and chemical composition of samples. The study focuses on intervertebral disc (IVD) tissue; however, it can be applied to other soft tissues. Raman spectroscopy synchronized with nanoindentation instrumentation was employed to investigate the compositional changes of IVD, specifically, nucleus pulposus (NP) and annulus fibrosus (AF), together with their biomechanical properties of IVD. These properties were examined through the following histological specimen types: fresh cryosection (control), fixed cryosection, and paraffin-embedded. The IVD tissue could be located using an optical microscope under three different preparation methods. Paraffin-embedded samples showed the most explicit details where the lamellae structure of AF could be identified. In terms of biomechanical properties, there was no significant difference between the fresh and fixed cryosection (p > 0.05). In contrast, the fresh cryosection and paraffin-embedded samples showed a significant difference (p < 0.05). It was also found that the tissue preparations affected the chemical content of the tissues and structure of the tissue, which are expected to contribute to biomechanical properties changes. Fresh cryosection and fixed cryosection samples are more promising to work with for biomechanical assessment in histological tissues. The findings fill essential gaps in the literature by providing valuable insight into the characteristics of IVD at the microscale. This study can also become a reference for a better approach to assessing the mechanical properties and chemical content of soft tissues at the microscale.