Degenerative Intervertebral Disc Disease Research Articles

Nutrient deprivation induces apoptosis of nucleus pulposus cells via activation of the BNIP3/AIF signalling pathway.

Nutrient deprivation (ND)-induced nucleus pulposus (NP) cell death serves an important role in intervertebral disc degeneration disease. However, the underlying mechanisms have yet to be thoroughly elucidated. The present study created a cell culture model under ND conditions to investigate the roles of the nutrient-sensitive protein B-cell lymphoma 2/adenovirus E1B 19 kDa-interacting protein (BNIP3) and the mitochondrial pro-death protein apoptosis-inducing factor (AIF) in the death pathway of NP cells. The present study demonstrated that cells subjected to ND for up to 72 h exhibited a time-dependent increase in cell death and decrease in mitochondrial membrane potential (Δψm), as compared with cells cultured under normal conditions. The results of western blotting demonstrated that BNIP3 expression was significantly upregulated in NP cells subjected to ND for 24 h, which coincided with AIF translocation to the cell nucleus and alterations in cell viability and Δψm. Furthermore, BNIP3 overexpression increased ND-induced NP cell death, whereas knockdown of BNIP3 or AIF abolished ND-induced NP cell death. In addition, BNIP3 overexpression increased AIF expression and BNIP3 knockdown decreased AIF expression in NP cells subjected to ND. In conclusion, ND induced NP cell death partially via activation of the BNIP3/AIF signalling pathway. These findings provide novel insights into the potential mechanisms underlying ND-induced death of NP cells during disc degeneration.

Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.

3D characterization of morphological changes in the intervertebral disc and endplate during aging: A propagation phase contrast synchrotron micro-tomography study

A better understanding of functional changes in the intervertebral disc (IVD) and interaction with endplate is essential to elucidate the pathogenesis of IVD degeneration disease (IDDD). To date, the simultaneous depiction of 3D micro-architectural changes of endplate with aging and interaction with IVD remains a technical challenge. We aim to characterize the 3D morphology changes of endplate and IVD during aging using PPCST. The lumbar vertebral level 4/5 IVDs harvested from 15-day-, 4- and 24-month-old mice were initially evaluated by PPCST with histological sections subsequently analyzed to confirm the imaging efficiency. Quantitative assessments of age-related trends after aging, including mean diameter, volume fraction and connectivity of the canals, and endplate porosity and thickness, reached a peak at 4 months and significantly decreased at 24 months. The IVD volume consistently exhibited same trend of variation with the endplate after aging. In this study, PPCST simultaneously provided comprehensive details of 3D morphological changes of the IVD and canal network in the endplate and the interaction after aging. The results suggest that PPCST has the potential to provide a new platform for attaining a deeper insight into the pathogenesis of IDDD, providing potential therapeutic targets.

Early-stage autophagy protects nucleus pulposus cells from glucose deprivation-induced degeneration via the p-eIF2α/ATF4 pathway.

Autophagy is a double-edged sword in cellular survival, but its effects on nucleus pulposus (NP) cells are yet to be clarified. This study explored the role and molecular mechanisms of autophagy in the survival of NP cells under nutrient deprivation. Glucose limitation induced time-dependent morphological changes, proteoglycan degradation, and apoptosis in NP cells. Glucose deprivation triggered the activation of early-stage autophagy, evident as increases in LC3-II and ATG12-ATG5 expression and the number of GFP-LC3 puncta. Importantly, at early time points, the autophagy inhibitor 3-MA significantly enhanced the apoptosis of NP cells, suggesting that early-stage autophagy protects cells against glucose deprivation. Interestingly, the p-eIF2α/ATF4 unfolded protein response pathway was activated in NP cells deprived of glucose, and a deficiency in ATF4 attenuated the activation of early-stage autophagy and increased apoptosis. ATF4 silencing also inhibited the late-stage accumulation of reactive oxygen species (ROS) and apoptosis. Together, our results demonstrate an interplay between endoplasmic reticulum stress, ROS production, and the early-stage autophagy induced by glucose deprivation in NP cells. These findings may provide a therapeutic strategy for the treatment of degenerative intervertebral disc disease.

A Review of the Degenerative Intervertebral Disc Disease

A Review of the Degenerative Intervertebral Disc Disease

Genetic risk factors of degenerative intervertebral disc disease: a case-control study

Background: The etiology of degenerative disc disease (DDD) is complex and includes genetic, gender, age, environment and traumatic factors. Obvious relatedness of DDD patients has been documented. Genetic factors account for 75% of the risk of DDD and although many genes have been associated with DDD, no specific marker genes have been found. Therefore, we will establish a biological sample library and database of DDD patients who have a family history of the disease and who require surgical treatment. To identify pathogenic DDD genes, we will screen the patient database for genes that contain polymorphisms and/or are differentially expressed. Methods/Design: This is a single-center, case-control study, which will be performed in Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, China. A total of 2,000 subjects will be prospectively collected from the wards and clinics of Shanghai First People's Hospital. These patients will consist of 1,000 DDD patients with a family history, 500 DDD patients without a family history, and 500 normal controls. Blood or intervertebral disc tissue samples will be collected. Total RNA will be sequenced to identify differentially expressed genes. Genome-wide association analysis will be performed using high-throughput microarrays and single nucleotide polymorphism microarrays and pooling (SNP-MAP). The primary outcome measure of this study will be the percentage of differentially expressed genes in DDD patients with or without a family history. The secondary outcome measures will be sequence variation in differentially expressed genes, SNP genotyping, routine liver and kidney function tests, routine blood tests, routine urine tests, and morphology of degenerated spinal discs. Discussion: This study aims to identify the pathological and physiological risk factors of DDD from the perspective of genetics by screening for genes that are differentially expressed in DDD and to correlate them with DDD, and to identify precise molecular targets for drug development and diagnostics. Trial registration: The study protocol was registered in Chinese Clinical Trial Registry (registration number: ChiCTR-COC-16009617) on October 10 th , 2016. Ethics: This study has been approved by Scientific Research Project Ethics Committee, Shanghai First People's Hospital, China (approval number: 2016KY166-2) and will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Informed consent: Written informed consent regarding study protocol and treatment procedure will be obtained prior to involvement in the clinical trial.

Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration.

ObjectivesInterleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration.MethodsLevels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.ResultsThe serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration.ConclusionsBMP-2 is anti-catabolic in human NP and AF cells, and its effects are partially mediated through provocation of the catabolic effect of IL-18. These findings indicate that BMP-2 may be a unique therapeutic option for prevention and reversal of disc degeneration.Cite this article: S. Ye, B. Ju, H. Wang, K-B. Lee. Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res 2016;5:412–418. DOI: 10.1302/2046-3758.59.BJR-2016-0032.R1.

The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration

ObjectivesThe circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However,...

Radiological, Histological and Biochemical Characterization of a Novel Ovine Lumbar Intervertebral Disc Injury Model

Introduction Numerous animal models of degenerative disc disease exist. Debate exists as to the ideal animal model and optimal method of inducing degeneration. The ovine lumbar spine is one accepted animal model of degenerative intervertebral disc disease. The goal of this study is to describe and characterize a novel, simple, reproducible ovine disc-injury model utilizing a drill bit inserted into the lumbar intervertebral disc to mimic disc degeneration. Material and Methods Six female sheep underwent pre-operative MRI followed by lumbar intervertebral disc injury at two levels via insertion of a 3.5mm diameter drill bit to a depth of 12 mm via a lateral retroperitoneal approach. Necropsies were performed two months following injury. Lumbar spines were explanted and underwent 9.4T MRI, radiographic imaging, gross morphological, histological and biochemical analysis. Gross morphologic assessment consisted of horizontal section of the intervertebral disc, digital photography of the surfaces. Biochemical analysis was performed for sulphated glycosaminoglycans, type I and type II collagen and DNA. Histological analysis utilized a semiquantitative grading system. Results There was no evidence of disc degeneration on pre-operative MRI. Drill bit injured discs demonstrated increased Pfirrmann degenerative scores relative to controls and pre-operative scores. Injured levels demonstrated significantly greater reductions in Disc Height Index than control levels. Gross morphological assessment similarly revealed significantly higher degenerative morphological scores in injured disc relative to pre-operative scores and controls. On biochemical analysis the annulus fibrosus (AF) at the entry point in injured discs contained less type II collagen and proteoglycans than the AF of non-injured control discs. Histological assessment demonstrated increased degenerative scores in injured disc on semiquantitative scoring. Conclusion These finding demonstrate that the 3.5mm drill bit ovine lumbar intervertebral-disc injury model produced macroscopic, radiological, biochemical and histological changes consistent with disc degeneration.

MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNA molecules, which regulate the gene expression at the post-transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease.

Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells.

IntroductionNutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells.MethodsThirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting.ResultsCells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II.ConclusionsSIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease.

Development of a whole organ culture model for intervertebral disc disease

SummaryBackground/ObjectiveWhole organ in vitro intervertebral disc models have been associated with poor maintenance of cell viability. No previous studies have used a rotating wall vessel bioreactor for intervertebral disc explants culture. The purpose of this study was to develop and validate an in vitro model for the assessment of biological and biomechanical measures of intervertebral disc health and disease.MethodsTo this end, endplate-intervertebral disc-endplate whole organ explants were harvested from the tails of rats. For the injured group, the annulus fibrosus was penetrated with a 20G needle to the nucleus pulposus and aspirated. Explants were cultured in a rotating wall vessel bioreactor for 14 days.ResultsCell viability and histologic assessments were performed at Day 0, Day 1, Day 7, and Day 14. Compressive mechanical properties of the intervertebral disc were assessed at Day 0 and Day 14. In the annulus fibrosus and nucleus pulposus cells, the uninjured group maintained high viability through 14 days of culture, whereas cell viability in annulus fibrosus and nucleus pulposus of the injured intervertebral discs was markedly lower at Day 7 and Day 14. Histologically, the uninjured intervertebral discs maintained cell viability and tissue morphology and architecture through 14 days, whereas the injured intervertebral discs showed areas of cell death, loss of extracellular matrix integrity, and architecture by Day 14. Stiffness values for uninjured intervertebral discs were similar at Day 0 and Day 14, whereas the stiffness for the injured intervertebral discs was approximately 2.5 times greater at Day 14.ConclusionThese results suggest that whole organ intervertebral discs explants can be successfully cultured in a rotating wall vessel bioreactor to maintain cell viability and tissue architecture in both annulus fibrosus and nucleus pulposus for at least 14 days. In addition, the injury used produced pathologic changes consistent with those seen in degenerative intervertebral disc disease in humans. This model will permit further study into potential future treatments and other mechanisms of addressing intervertebral disc disease.

Thymosin Beta-4 Recombinant Adeno-associated Virus Enhances Human Nucleus Pulposus Cell Proliferation and Reduces Cell Apoptosis and Senescence.

Background:Thymosin beta-4 (TB-4) is considered key roles in tissue development, maintenance and pathological processes. The study aimed to prove TB-4 positive biological function on nucleus pulposus (NP) cell apoptosis and slowing the process of cell aging while increasing the cell proliferation.Methods:TB-4 recombinant adeno-associated virus (AAV) was constructed and induced to human NP cells. Cell of same group were cultured without gene modification as controlled group. Proliferation capacity and cell apoptosis were observed during 6 passages of the cells. Morphology and expression of the TB-4 gene were documented as parameter of cell activity during cell passage.Results:NP cells with TB-4 transfection has normal TB-4 expression and exocytosis. NP cells with TB-4 transfection performed significantly higher cell activity than that at the control group in each generation. TB-4 recombinant AAV-transfected human NP cells also show slower cell aging, lower cell apoptosis and higher cell proliferation than control group.Conclusions:TB-4 can prevent NP cell apoptosis, slow NP cell aging and promote NP cell proliferation. AAV transfection technique was able to highly and stably express TB-4 in human NP cells, which may provide a new pathway for innovation in the treatment of intervertebral disc degenerative diseases.

Mesenchymal stem cells for intervertebral disc repair and regeneration

Low back pain secondary to degenerative intervertebral disc disease contributes to significant pain and disability in the United States. The potential to reverse intervertebral disc degeneration has driven significant interest in the development of stem cell therapy for degenerative disc disease. Early animal models have demonstrated that stem cell therapy may facilitate the reversal of the disc degeneration. The aim of this study is to review the currently available literature on MSC technology and its use in intervertebral disc repair and regeneration.

Determination of the potential of induced pluripotent stem cells to differentiate into mouse nucleus pulposus cells in vitro.

We determined the potential for induced pluripotent stem (iPS) cells to differentiate into nucleus pulposus (NP)-like cells in mice. iPS cells were generated from tail-tip fibroblasts. We used a pellet culture model with the aim of determining the applicability of iPS cell-based therapy to intervertebral disc degeneration (IVD). The cell pellet was cultured in an NP cell basal medium comprising Dulbecco's modified Eagle's medium supplemented with transforming growth factor beta 1, dexamethasone, ascorbate-2-phosphate, and 1% ITS-Premix. The pellet was evaluated by quantitative reverse transcription polymerase chain reaction, immunohistochemical staining, and biochemical composition. The differentiation of iPS cells into NP cells was demonstrated by the protein and mRNA expression levels of proteoglycan, collagen II, aggrecan, and CD24. Furthermore, increased hydroxyproline content and dimethylmethylene blue staining demonstrated that the collagen II and glycosaminoglycan content in the NP cells increased with time. We have shown that cultured mouse iPS cells can be induced to differentiate into NP cells. Such proof-of-concept opens up the possibility of producing patient-specific NP cells in a relatively simple and straightforward manner with high efficiency. We are confident that such cells could be immediately useful for the study of IVD disease.

LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression.

Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF-α induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LV-shLMP-1 aggravated TNF-α mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-α induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-κB inhibition.

Role of the mitochondrial pathway in serum deprivation-induced apoptosis of rat endplate cells

The apoptosis of cartilage endplates (CEPs), acting as an initiating factor, plays a vital role in the pathogenesis of intervertebral disc degenerative diseases, the underlying molecular mechanism of the apoptotic process in CEPs is still not clear. The present study aimed to investigate the mechanism of CEP cell apoptosis. We found that low levels of fetal bovine serum (FBS) can induce cell apoptosis. Serum deprivation led to high expression levels of caspase-9, caspase-3, PARP, cytochrome-c and Bax. Flow cytometric analysis showed that inhibition of the intrinsic pathway by a caspase-9 inhibitor (z-LEHD-fmk) significantly suppressed serum deprivation-induced apoptosis. However, a caspase-8 inhibitor (z-IETD-fmk) did not reduce apoptotic cell death. These data suggest that serum deprivation induces apoptosis in rat CEP cells via the activation of the intrinsic apoptotic pathway. The efficacy of a caspase-9 inhibitor in attenuating or preventing apoptosis of serum deprivation-induced disc cell apoptosis suggests that targeting the intrinsic apoptotic pathway may be used as a potential therapy for the treatment of disc degeneration.

Disseminated idiopathic skeletal hyperostosis: diagnostic criteria and clinical significance

DISSEMINATED idiopathic skeletal hyperostosis (DISH) is a systemic disorder of the axial and appendicular skeleton characterised by calcification and ossification in soft tissues, including the spinal ventral longitudinal ligament and...

PDGF-BB inhibits intervertebral disc cell apoptosis in vitro.

Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures. The anti-apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF-treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT-PCR, respectively. We found that rhPDGF-BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti-degenerative effects of rhPDGF-BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF-BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF-BB may be used as a biologic treatment to target early degenerative IVD disease in the future.

Computer aided diagnosis of degenerative intervertebral disc diseases from lumbar MR images

This paper presents a novel method for the automated diagnosis of the degenerative intervertebral disc disease in midsagittal MR images. The approach is based on combining distinct disc features under a machine learning framework. The discs in the lumbar MR images are first localized and segmented. Then, intensity, shape, context, and texture features of the discs are extracted with various techniques. A Support Vector Machine classifier is applied to classify the discs as normal or degenerated. The method is tested and validated on a clinical lumbar spine dataset containing 102 subjects and the results are comparable to the state of the art.