Diagnosis Of Intervertebral Disc Degeneration Research Articles

Role of Autophagy and Pyroptosis in Intervertebral Disc Degeneration.

Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.

Automatic Detection, Classification, and Grading of Lumbar Intervertebral Disc Degeneration Using an Artificial Neural Network Model.

Intervertebral disc degeneration (IDD) is a common cause of symptomatic axial low back pain. Magnetic resonance imaging (MRI) is currently the standard for the investigation and diagnosis of IDD. Deep learning artificial intelligence models represent a potential tool for rapidly and automatically detecting and visualizing IDD. This study investigated the use of deep convolutional neural networks (CNNs) for the detection, classification, and grading of IDD. Sagittal images of 1000 IDD T2-weighted MRI images from 515 adult patients with symptomatic low back pain were separated into 800 MRI images using annotation techniques to create a training dataset (80%) and 200 MRI images to create a test dataset (20%). The training dataset was cleaned, labeled, and annotated by a radiologist. All lumbar discs were classified for disc degeneration based on the Pfirrmann grading system. The deep learning CNN model was used for training in detecting and grading IDD. The results of the training with the CNN model were verified by testing the grading of the dataset using an automatic model. The training dataset of the sagittal intervertebral disc lumbar MRI images found 220 IDDs of grade I, 530 of grade II, 170 of grade III, 160 of grade IV, and 20 of grade V. The deep CNN model was able to detect and classify lumbar IDD with an accuracy of more than 95%. The deep CNN model can reliably automatically grade routine T2-weighted MRIs using the Pfirrmann grading system, providing a quick and efficient method for lumbar IDD classification.

Comprehensive Network Analysis Identified SIRT7, NTRK2, and CHI3L1 as New Potential Markers for Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is considered the basis of serious clinical symptoms, especially for low back pain (LBP). Therefore, it is essential to explore the regulatory role and diagnostic performance of dysregulated genes and potential drugs in IDD. Through WGCNA co-expression analysis, 36 co-expression modules were obtained. Among them, MidnightBlue and Red modules were the most related to IDD. Functional enrichment analysis showed that the Red module was mainly related to neutrophil activation and regulation of cytokine-mediated signaling pathway and apoptosis, whereas the MidnightBlue module was mainly related to extracellular matrix organization, bone development, extracellular matrix, extracellular matrix component, and other extracellular matrices. Furthermore, 356 genes highly related to the module were screened to construct a protein interaction network. Network degree distribution analysis showed that the known IDD-related genes had a higher degree of distribution. Enrichment analysis demonstrated that these genes were enriched in MAPK_SIGNALING_PATHWAY (FDR = 0.012), CHEMOKINE_SIGNALING_PATHWAY, and some other pathways. By constructing a disease-gene interaction network, three disease-specific genes were finally identified. Through combining with the drug-target gene interaction network, two potential therapeutic drugs, entrectinib and larotrectinib, were determined. Finally, based on these genes, the diagnostic model in the training dataset, test dataset, and verification dataset all showed a high diagnostic performance. The findings of this study contributed to the diagnosis of IDD and personalized treatment of IDD.

A Study on COMP and CTX-II as Molecular Markers for the Diagnosis of Intervertebral Disc Degeneration.

Background Diagnosis of intervertebral disc degeneration (IVDD) is challenging at the early stage. The cartilage oligomeric matrix protein (COMP) and extracellular matrix degradation products of C-telopeptide of type II collagen (CTX-II) serve as markers for the serological diagnosis of IVDD. Oxidative stress might cause IVDD and matrix degeneration. Methods A total of 128 male adult Sprague–Dawley (SD) rats were randomly and equally assigned to the experimental and control groups. The experimental group was used to construct IVDD models by acupuncture, while the control group underwent sham operation. The animals were executed every week for 8 weeks after intervertebral disc acupuncture, and serum samples were collected for the estimation of CTX-II and COMP concentrations by enzyme-linked immunosorbent assay (ELISA). Also, the histological changes and caudal magnetic resonance imaging (MRI) changes were examined in the intervertebral disc. Results IVDD in rats worsened with prolonged follow-up after acupuncture. At all the time points, the experimental group showed altered histological and caudal vertebra MRI signals, and serum CTX-II and COMP concentrations were significantly greater than those of the control group. These levels increase with the process of IVDD. Conclusion Serum CTX-II and COMP estimation is a reliable method to diagnose IVDD, and their concentrations show a positive correlation with the process of IVDD.

Role of microRNAs in intervertebral disc degeneration (Review).

The incidence of lower back pain caused by intervertebral disc degeneration (IDD) is gradually increasing. IDD not only affects the quality of life of the patients, but also poses a major socioeconomic burden. There is currently no optimal method for delaying or reversing IDD, mainly due to its unknown pathogenesis. MicroRNAs (miRNAs/miRs) participate in the development of a number of diseases, including IDD. Abnormal expression of miRNAs in the intervertebral disc is implicated in various pathological processes underlying the development of IDD, including nucleus pulposus (NP) cell (NPC) proliferation, NPC apoptosis, extracellular matrix remodeling, inflammation and cartilaginous endplate changes, among others. The focus of the present review was the advances in research on the involvement of miRNAs in the mechanism underlying IDD. Further research is expected to identify markers for early diagnosis of IDD and new targets for delaying or reversing IDD.

Evaluation of Cartilaginous Endplate Degeneration Based on Magnetic Resonance Imaging.

In order to carry out the evaluation of cartilaginous endplate degeneration based on magnetic resonance imaging (MRI), this paper retrospectively analyzed the MRI data from 120 cases of patients who were diagnosed as lumbar intervertebral disc degeneration and underwent MRI examinations in the designated hospital of this study from June 2018 to June 2020. All cases underwent conventional sagittal and transverse T1WI and T2WI scans, and some cases were added with sagittal fat-suppression T2WI scans; then, the number of degenerative cartilaginous endplates and its ratio to degenerative lumbar intervertebral discs were counted and calculated, and the T1WI and T2WI signal characteristics of each degenerative cartilage endplate and its correlation with cartilaginous endplate degeneration were summarized, compared, and analyzed to evaluate the cartilaginous endplate degeneration by those magnetic resonance information. The study results show that there were 33 cases of cartilaginous endplate degeneration, accounting for 27.50% of all those 120 patients with lumbar intervertebral disc degeneration (54 degenerative endplates in total), including 9 cases with low T1WI and high T2WI signals, 5 cases with high T1WI and low T2WI signals, 12 cases with high and low mixed T1WI and high or mixed T2WI signals, and 4 cases with both low T1WI and T2WI signals. Therefore, MRI scanning can clearly present the abnormal signals of lumbar intervertebral disc and cartilaginous endplate degeneration, accurately identity their lesion locations, and type their degenerative characteristics, which may be best inspection method for the evaluation of cartilaginous endplate degeneration in the early diagnosis of intervertebral disc degeneration. The study results of this paper provide a reference for further researches on the evaluation of cartilaginous endplate degeneration based on magnetic resonance imaging.

Roles of miR-182 in Intervertebral Disc Degeneration and its Potential Prognostic Value

MicroRNAs were reported to be involved in the progression of intervertebral disc degeneration (IDD). This study focused on the potential prognostic value and the underlying mechanism of miR-182 in IDD. The expression level of miR-182 in plasma samples from 60 IDD patients and 60 healthy controls were examined in the present study. Then, the relationship between miR-182 expression and clinical features of IDD patients was analyzed. Moreover, the nucleus pulposus (NP) cells were cultured and transfected with either miR-182 inhibitor, mimics, or NC to explore the effects of miR-182 on cell proliferation and apoptosis. Furthermore, expression levels of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3 were also evaluated. The expression level of miR-182 was dramatically increased in plasma samples of IDD patients compared with the controls. Moreover, ROC analysis indicated that miR-182 was a feasible diagnostic indicator for the diagnosis of IDD. According to the Japanese Orthopaedic Association (JOA) score, the prognosis of patients with the lower expression levels of miR-182 was better than for those with the higher expression levels of miR-182 in IDD. Furthermore, the miR-182 inhibitor significantly increased the proliferation, decreased the apoptosis of human NP cells, and altered the expression of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3. On the contrary, miR-182 mimics notably inhibited proliferation but promoted apoptosis of human NP cells and increased Bax and Caspase-3 expressions while reducing the Bcl-2 level. miR-182 was negatively correlated with the prognosis of the IDD patients and affected the proliferation and apoptosis of NP cells in vitro.

Application of magnetic resonance T2 -mapping imaging in quantitative detection of early intervertebral disc degeneration in obese people

Objective To explore the clinical value of magnetic resonance T2-mapping imaging in the diagnosis of early intervertebral disc degeneration in obese people. Methods From January 2018 to June 2019, 30 obese volunteers and 30 healthy volunteers with normal weight underwent T2-mapping scan, while their routine MRI examination showed no abnormalities were slected.The T2 value of nucleus pulposus in both two groups were measured and compared. Results The T2 values of nucleus pulposus of intervertebral disc of lumbar 1-2, lumbar 2-3, lumbar 3-4, lumbar 4-5 and lumbar 5-sacral 1 in the control group were (108.17±10.87)ms, (113.93±11.54)ms, (126.65±10.22)ms, (118.62±8.86)ms and (111.61±10.65)ms, respectively, which of nucleus pulposus in different segments was statistically significant(F=14.28, P<0.001). The T2 values of nucleus pulposus of intervertebral disc of lumbar 1-2, lumbar 2-3, lumbar 3-4, lumbar 4-5, lumbar 5-sacral 1 in the simple obesity group were (104.90±7.67)ms, (101.10±6.61)ms, (112.65±5.75)ms, (98.27±6.18)ms, (89.82±6.34)ms, respectively, , which of nucleus pulposus in different segments was statistically significant(F=49.52, P<0.001). There were statistically significant differences in the T2 values of nucleus pulposus of intervertebral disc of lumbar 2-3, lumbar 3-4, lumbar 4-5, lumbar 5-sacral 1 between the two groups(t=5.283, 6.535, 10.327, 9.626, all P<0.001). Conclusion Magnetic resonance T2-mapping can detect early changes in tissue composition of intervertebral disc degeneration.Therefore, magnetic resonance T2-mapping imaging technology can provide an important reference for the early diagnosis of intervertebral disc degeneration in obese people. Key words: Magnetic resonance imaging; T2-mapping; Quantitative detection; Intervertebral disc degeneration; Intervertebtal disk; Lumbar vertebrae; Obesity

Feasibility of T2 Mapping and Magnetic Transfer Ratio for Diagnosis of Intervertebral Disc Degeneration at the Cervicothoracic Junction: A Pilot Study

Background Intervertebral disc degeneration (IDD) at the cervicothoracic junction of spine is clinically relevant, however, little attention had been paid. T2 mapping and magnetic transfer ratio (MTR) are useful magnetic resonance imaging (MRI) techniques to quantitatively evaluate IDD, revealing the biochemical changes within the intervertebral disc. To compare T2 mapping with MTR imaging regarding their accuracy to quantitatively diagnose intervertebral disc degeneration at the cervicothoracic junction, influences of anatomical level, gender, age, and Pfirrmann grade of T2 relaxation time values and MTR values were evaluated. Methods Sixty-seven patients with neck and upper back pain were included and examined with both T2 mapping and MTR imaging. The Pfirrmann grade, T2 relaxation time values, and MTR value of each disc between C7 and T3 were measured. Differences were investigated among different segmental levels, genders, age ranges, and Pfirrmann grades. The diagnostic accuracy of both MRI techniques was compared using the receiver operating characteristic (ROC) curves. Results No significant difference was detected comparing T2 relaxation time values or MTR values among different anatomical levels, genders, and segmental levels. And we generally found that T2 relaxation time values decreased, while MTR value increased with increasing age. Importantly, we demonstrated the significant correlation between either T2 relaxation time values or MTR value and Pfirrmann grade. Conclusion We proved the better accuracy of T2 mapping over MTR imaging to quantitatively evaluate the intervertebral disc degeneration of the cervicothoracic junction.

Changes in MRI Parameters of Porcine Intervertebral Discs under Compressive Loading

Intervertebral disc (IVD) is a major source of Low Back Pain (LBP). The health and functions of the IVD are determined by the inherent biomechanical properties and their interaction with external loading. Recent advances in quantitative Magnetic Resonance Imaging (MRI) techniques have the potential in detecting loading-induced changes in the biomechanical properties of the IVD. Twenty functional spinal units (FSU) from porcine cervical spines were imaged with a 7T scanner to obtain T1ρ, T2 and Apparent Diffusion Coefficient (ADC) before and after experiencing compressive loading of 263.27N for 60 minutes. Compressive loading was found to significantly decrease T1ρ and T2 but not ADC, which indicated that T1ρ and T2 had the potential to detect changes in the biomechanical properties of the IVD due to external loading. These parameters may provide more sensitivity and specificity to understand the injury mechanism of the IVD and contribute to early diagnosis of IVD degeneration.

Long non‑coding RNA FAF1 promotes intervertebral disc degeneration by targeting the Erk signaling pathway.

Intervertebral disc degeneration (IDD) has become the most common cause of low‑back pain, and it imposes a heavy burden on patients with IDD and society. The effects of long non‑coding RNAs on the proliferation and development of IDD have attracted increasing attention. The present study aimed to investigate the role and molecular mechanism of Fas‑associated protein factor‑1 (FAF1) in IDD. The expression of FAF1 was detected by reverse transcription‑quantitative polymerase chain reaction. CCK‑8 and immunofluorescence staining were used to determine cell proliferation. Flow cytometry was performed to measure the cell cycle and apoptosis. Western blotting was used to test p‑Erk expression. The results of the present study demonstrated that the expression of FAF1 was upregulated in patients with disc bulging, herniation and IDD, and the expression of FAF1 was positively correlated with the grade of disc degeneration according to the patients' Pfirrmann score. The overexpression of FAF1 in nucleus pulposus (NP) cells promoted cell proliferation by increasing the percentage of cells in the S‑phase of the cell cycle. The expression of phosphorylated extracellular signal‑regulated kinase (Erk), a possible target of FAF1, was consistent with the expression of FAF1. In addition, it was elucidated that inactivation of the Erk signaling pathway by PD98059 reversed the effect of FAF1 on NP cell proliferation. Taken together, these results demonstrated that FAF1 was vital in the proliferation of NP cells by modulating the Erk signaling pathway, which suggests that FAF1 may be a novel marker in the early diagnosis of IDD and a therapeutic target for patients.

Multimodal quantitative magnetic resonance imaging for lumbar intervertebral disc degeneration.

The present study investigated the application of the T1ρ and T2 relaxation mapping magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the evaluation of intervertebral disc degeneration (IDD). A total of 93 asymptomatic subjects were imaged with T1ρ and T2 mapping, as well as DWI. Pfirrmann grading was performed and correlation analysis was conducted for T1ρ, T2 and DWI results with the grading results and age. Pfirrmann grading indicated 69 cases of grade I, 240 cases of grade II, 101 cases of grade III, 43 cases of grade IV and 12 cases of grade V. MRI showed that the T1ρ values of the nucleus pulposi at L4/5 and L5/S1 were significantly reduced (P<0.05) and no significant differences were observed in the T2 values compared with the values of the nucleus pulposus at L1/2, L2/3 and L3/4. The apparent diffusion coefficient (ADC) values of L1/2 were significantly decreased from L2/3 and L3/4 (P<0.05). Correlation analysis revealed that the T1ρ, T, and ADC values were positively correlated with each other. Moreover, the T1ρvalues were significantly decreased with the increase of Pfirrmann grades (P<0.05), with the exception of grades IV and V. However, T2 and ADC values were not significantly different between grades I and II or IV and V. In addition, the T1ρ, T2 and ADC values were significantly decreased with the increase of age in patients with IDD (P<0.05). T1ρ and T2 mapping and DWI are promising techniques for the in vivo diagnosis of IDD, which may be useful in determining the appropriate prevention and treatment options for the disease.

Functional probe for annulus fibrosus-targeted intervertebral disc degeneration imaging

Intervertebral disc degeneration (IDD) is closely associated with low back pain. Typically nonsurgical treatment of IDD is the most effective when detected early. As such, establishing reliable imaging methods for the early diagnosis of disc degeneration is critical. The cellular and tissue localization of a facile functional fluorescent probe, HYK52, that labels disc annulus fibrosus is reported. HYK52 was synthesized with high yield and purity via a two-step chemical reaction. Rabbit disc cell studies and ex vivo tissue staining images indicated intracellular localization and intervertebral disc (IVD) tissue binding of HYK52 with negligible cytotoxicity. Moreover, HYK52 is purposefully designed with a functional terminal carboxyl group to allow for coupling with various signaling molecules for multimodal imaging applications. These results suggest that this IVD-targeted probe may have great potential in early diagnosis of IDD.