Feature Of Intervertebral Disc Degeneration Research Articles

ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.

Extracellular matrix metabolism dysregulation in nucleus pulposus (NP) cells represents a crucial pathophysiological feature of intervertebral disc degeneration (IDD). Our study elucidates the role and mechanism of Testis expressed 11 (TEX11, also called ZIP4) extracellular matrix degradation in the NP. Interleukin-1β (IL-1β) and H2O2 were used to treat NP cells to establish an IDD cell model. Normal NP tissues and NP tissues from IDD patients were harvested. ZIP4 mRNA and protein profiles in NP cells and tissues were examined. Enzyme-linked immunosorbent assay (ELISA) confirmed the profiles of TNF-α, IL-6, MDA, and SOD in NP cells. The alterations of reactive oxygen species (ROS), lactate dehydrogenase (LDH), COX2, iNOS, MMP-3, MMP-13, collagen II, aggrecan, FoxO3a, histone deacetylase 4 (HDAC4), Sirt1 and NF-κB levels in NP cells were determined using different assays. The ZIP4 profile increased in the NP tissues of IDD patients and IL-1β- or H2O2-treated NP cells. ZIP4 upregulation bolstered inflammation and oxidative stress in NP cells undergoing IL-1β treatment and exacerbated their extracellular matrix degradation, whereas ZIP4 knockdown produced the opposite outcome. Mechanistically, ZIP4 upregulated HDAC4 and enhanced NF-κB phosphorylation while repressing Sirt1 and FoxO3a phosphorylation levels. HDAC4 knockdown or Sirt1 promotion attenuated the effects mediated by ZIP4 overexpression in NP cells. ZIP4 upregulation aggravates the extracellular matrix (ECM) degradation of NP cells by mediating inflammation and oxidative stress through the HDAC4-FoxO3a axis.

Cell clusters in intervertebral disc degeneration: an attempted repair mechanism aborted via apoptosis.

Cell clusters are a histological hallmark feature of intervertebral disc degeneration. Clusters arise from cell proliferation, are associated with replicative senescence, and remain metabolically, but their precise role in various stages of disc degeneration remain obscure. The aim of this study was therefore to investigate small, medium, and large size cell-clusters. For this purpose, human disc samples were collected from 55 subjects, aged 37-72 years, 21 patients had disc herniation, 10 had degenerated non-herniated discs, and 9 had degenerative scoliosis with spinal curvature <45°. 15 non-degenerated control discs were from cadavers. Clusters and matrix changes were investigated with histology, immunohistochemistry, and Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Data obtained were analyzed with spearman rank correlation and ANOVA. Results revealed, small and medium-sized clusters were positive for cell proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) in control and slightly degenerated human discs, while large cell clusters were typically more abundant in severely degenerated and herniated discs. Large clusters associated with matrix fissures, proteoglycan loss, matrix metalloproteinase-1 (MMP-1), and Caspase-3. Spatial association findings were reconfirmed with SDS-PAGE that showed presence to these target markers based on its molecular weight. Controls, slightly degenerated discs showed smaller clusters, less proteoglycan loss, MMP-1, and Caspase-3. In conclusion, cell clusters in the early stages of degeneration could be indicative of repair, however sustained loading increases large cell clusters especially around microscopic fissures that accelerates inflammatory catabolism and alters cellular metabolism, thus attempted repair process initiated by cell clusters fails and is aborted at least in part via apoptosis.

Bushen Huoxue Formula Modulates Autophagic Flux and Inhibits Apoptosis to Protect Nucleus Pulposus Cells by Restoring the AMPK/SIRT1 Pathway.

Background Low back pain (LBP) has the characteristics of chronic and persistence, which is a heavy social burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. The typical features of IVDD are extracellular matrix (ECM) degradation and nucleus pulposus cell (NP) apoptosis. Bushen Huoxue Formula (BSHXF) has good clinical effects on LBP. However, the mechanism of BSHXF affecting ECM and NP cells is still unclear. Aim of the Study. In this study, the impact of BSHXF on autophagy and apoptosis of NP cells was studied through the AMPK/SIRT1 pathway. Material and Methods. NP cells were extracted through the digestion of collagenase and trypsin, and the components of BSHXF were identified. Cell Counting Kit-8 was applied to detect the impact of BSHXF on NP cells. Mitochondrial function was detected using MitoTracker assay, ATP kit, and SOD kit. Autophagy and apoptosis were detected by RT-qPCR, western blotting, and flow cytometry. Results BSHXF promoted NP cell survival in a concentration-dependent manner, and the elimination of rat serum did not increase cell proliferation; TNF-α accelerated ECM degradation, ROS accumulation, and NP cell apoptosis and decreased autophagic flux. BSHXF restored mitochondrial function and autophagic flux. In addition, AMPK/SIRT1 pathway activation was associated with IVDD. Conclusions BSHXF regulates autophagy and enhances autophagic flux to suppress excessive ROS production and restore mitochondrial function in an AMPK/SIRT1-dependent manner. However, the protection of BSHXF on TNF-α-treated cells was eliminated by 3-MA. Furthermore, the protective impact of BSHXF on ECM degradation and apoptosis induced by TNF-α was restrained by an AMPK inhibitor. Therefore, maintaining the proper autophagy illustrates treatment strategy for IVDD.

Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain-related behavior.

BackgroundPrevious animal models of intervertebral disc degeneration (IDD) rely on open surgical approaches, which confound the degenerative response and pain behaviors due to injury to surrounding tissues during the surgical approach. To overcome these challenges, we developed a minimally invasive percutaneous puncture procedure to induce IDD in a rat model.MethodsTen Fischer 344 male rats underwent percutaneous annular puncture of lumbar intervertebral discs (IVDs) at L2‐3, L3‐4, and L4‐5. Ten unpunctured rats were used as controls. Magnetic resonance imagings (MRIs), serum biomarkers, and behavioral tests were performed at baseline and 6, 12, and 18 weeks post puncture. Rats were sacrificed at 18 weeks and disc histology, immunohistochemistry, and glycosaminoglycan (GAG) assays were performed.ResultsPunctured IVDs exhibited significant reductions in MRI signal intensity and disc volume. Disc histology, immunohistochemistry, and GAG assay results were consistent with features of IDD. IVD‐punctured rats demonstrated significant changes in pain‐related behaviors, including total distance moved, twitching frequency, and rearing duration.ConclusionsThis is the first reported study of the successful establishment of a reproducible rodent model of a percutaneous lumbar annular puncture resulting in discogenic pain. This model will be useful to test therapeutics and elucidate the basic mechanisms of IDD and discogenic pain.

Deep learning-based high-accuracy quantitation for lumbar intervertebral disc degeneration from MRI

To help doctors and patients evaluate lumbar intervertebral disc degeneration (IVDD) accurately and efficiently, we propose a segmentation network and a quantitation method for IVDD from T2MRI. A semantic segmentation network (BianqueNet) composed of three innovative modules achieves high-precision segmentation of IVDD-related regions. A quantitative method is used to calculate the signal intensity and geometric features of IVDD. Manual measurements have excellent agreement with automatic calculations, but the latter have better repeatability and efficiency. We investigate the relationship between IVDD parameters and demographic information (age, gender, position and IVDD grade) in a large population. Considering these parameters present strong correlation with IVDD grade, we establish a quantitative criterion for IVDD. This fully automated quantitation system for IVDD may provide more precise information for clinical practice, clinical trials, and mechanism investigation. It also would increase the number of patients that can be monitored.

AF cell derived exosomes regulate endothelial cell migration and inflammation: Implications for vascularization in intervertebral disc degeneration

AimsThe intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD. Main methodsHuman AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry. Key findingsHere, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects. SignificanceThese results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.

CDMP1 promotes type II collagen and aggrecan synthesis of nucleus pulposus cell via the mediation of ALK6.

Destruction of extracellular matrix (ECM), especially collagen II and aggrecan, is an essential feature of intervertebral disc degeneration (IDD). This project planned to elucidate the role of cartilage-derived morphogenetic protein-1 (CDMP-1) in the collagen II and aggrecan synthesis of nucleus pulposus (NP) cells under the IL-1β induced degeneration. We cultured human primary NP cells in the different concentrations of IL-1β medium and analyzed the CDMP-1 level. Recombinant human CDMP-1 protein was used to co-culture with IL-1β to investigate its effects on collagen II and aggrecan synthesis of NP cells. Additionally, the bone morphogenetic protein type IB receptor (ALK6) gene silenced and upregulated NP cells were used to evaluate the function of ALK6 in the CDMP-1 treated NP cells. Collagen II, aggrecan, MMP9, MMP13, and TIMP4 expression level were analyzed to assess the ECM stability of NP cells. CDMP-1 gene expression decreased in the IL-1β treated NP cells with a dose-dependent. Appropriate CDMP-1 protein supplement contributed to the collagen II and aggrecan production, the suppression of MMP9 and MMP13, and the upregulation of TIMP4. However, the silencing of ALK6 rejected the positive function of CDMP-1 on the collagen II and aggrecan; on the contrary, ALK6 upregulation magnified the CDMP-1 induced collagen II and aggrecan production. CDMP-1 is efficient in promoting the collagen II and aggrecan synthesis of NP cells, which is probably based on the mediation of ALK6.

SDF1/CXCR4 axis facilitates the angiogenesis via activating the PI3K/AKT pathway in degenerated discs.

Symptomatic degenerative disc disease (DDD) is considered the leading cause of chronic lower back pain (LBP). As one of the main features of intervertebral disc degeneration (IDD), vascular ingrowth plays a crucial role in the progression of LBP. Stromal cell-derived factor 1 (SDF1) and its receptor C-X-C receptor 4 (CXCR4) were reported to be overexpressed in the degenerated intervertebral discs, suggesting that they may be involved in the pathogenesis of IDD. Moreover, SDF1 has been identified to induce neovascularization in rheumatoid arthritis disease. However, the roles of the SDF1/CXCR4 axis in the neovascularization of IDD remain unclear. Therefore, the objective of the present study was to elucidate whether the SDF1/CXCR4 axis takes part in neovascularization in degenerated intervertebral discs and its underlying mechanisms. Adenovirus infection was used to upregulate SDF1 expression in primary nucleus pulposus cells (NPCs). The effects of SDF1 on the proliferation and angiogenesis of vascular endothelial cells (VECs) were assessed by Cell Counting Kit-8 and tube formation assays after VECs were treated with the supernatants derived from SDF1 overexpressed or not treated NPCs. Transwell chambers using the supernatants from NPCs as chemokines were applied to assess VEC migration and invasion. AMD3100, MK-2206 and SF1670 were used to antagonize CXCR4, AKT serine/threonine kinase 1 (AKT) and phosphatase and tensin homolog (PTEN) in VECs. The results revealed that SDF1 overexpression significantly increased the ratio of phosphorylated AKT to AKT and decreased PTEN expression in NPCs, as well as enhanced the proliferation, migration, invasion and angiogenesis abilities of VECs. However, these effects induced by SDF1 overexpression in NPCs were all reversed when VECs were pretreated with AMD3100 or MK-2206, whereas enhanced by SF1670 treatment. Collectively, the present study indicated that enhancement of the SDF1/CXCR4 axis in NPCs can significantly accelerate angiogenesis by regulating the PTEN/phosphatidylinositol-3-kinase/AKT pathway.

LncRNA TUG1 Promotes the Intervertebral Disc Degeneration and Nucleus Pulposus Cell Apoptosis Though Modulating miR-26a/HMGB1 Axis and Regulating NF-κB Activation

Background: The core feature of intervertebral disc degeneration (IDD) is the reduction in the number of nucleus pulposus cells (NPCs) and the loss of extracellular matrix (ECM). Emerging studies have shown that long-chain non-coding RNAs (lncRNAs) taurine upregulated gene 1 (TUG1) plays a key role in the development of IDD. However, the relevant mechanisms of TUG1 in the development of IDD are not yet clear. Objective: This study investigated the effect of TUG1 on apoptosis and ECM degradation of human degenerative intervertebral disc NPCs and its mechanism. Methods: The expression of TUG1 in the human IDD NP tissues and NPCs was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of overexpression or knockdown of TUG1 on cell proliferation and apoptosis were examined by EdU assay and flow cytometry, respectively. Utilizing bioinformatics methods, luciferase activity assay, the possible interacted miRNA and Mrna were explored. Western blot analysis determined the expression levels of collagen II, aggrecan, MMP-3 and MMP-13. Additionally, the effect of TUG1 on NF-κB pathway was analyzed by western blot assay and immunofluorescence staining. Results: The expression of TUG1 and HMGB1 protein in human degenerative disc NP tissues and NPCs was significantly increased, while the level of miR-26a was significantly decreased. Overexpression of TUG1 inhibited the proliferation while promoted apoptosis and ECM degradation of human degenerative intervertebral disc NPCs. Simultaneously, the effect of TUG1 knockdown on NPCs was opposite. Interestingly, TUG1 acts as an endogenous sponge to down-regulate the expression of miR-26a in NPCs by direct binding to miR-26a.Overexpression of miR-26a reversed the effect of TUG1 overexpression on apoptosis and ECM degradation. Additionally, HMGB1 is a target gene of miR-26a.The increased expression of HMGB1 induced by TUG1 overexpression can be reversed by the introduction of miR-26a mimic. Overexpression of TUG1 significantly upregulated the expression of p65 in the nucleus, and overexpression of TUG1 partially abolished the inhibition of NF-κB by NF-κB specific inhibitor QNZ pretreatment. Conclusion: TUG1 can promote the apoptosis and ECM degradation of degenerated intervertebral disc NPCs by regulating the miR-26a/HMGB1, which may be involved in the activation of NF-κB pathway. Funding Statement: The authors stated that no funding was received. Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: This study was approved by the Ethics Committee of Chinese Academy of Medical Sciences Peking Union Medical College Hospital.

Correlations Between COL2A and Aggrecan Genetic Polymorphisms and the Risk and Clinicopathological Features of Intervertebral Disc Degeneration in a Chinese Han Population: A Case-Control Study.

This case-control study was designed to evaluate the association of three COL2A1 single nucleotide polymorphism (SNPs) (rs1793953, rs2276454, and rs1793937) and Aggrecan variable number of tandem repeat (VNTR) polymorphisms with the risk and clinicopathological features of intervertebral disc degeneration (IVDD) in a Chinese Han population. Data from 295 IVDD patients (case group) and 324 healthy volunteers (control group) were collected between January 2012 and December 2014. Magnetic resonance examinations were conducted on all included subjects. The frequency distributions of the COL2A1 and Aggrecan polymorphisms were detected using direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The genotype and allele frequencies of the COL2A1 genetic polymorphisms (rs1793953 and rs2276454) and the Aggrecan VNTR polymorphisms differed significantly between the case group and the control group (all p < 0.05). The haplotype analysis indicated that the frequencies of ACGL (L, long) and GTCL haplotypes were lower in the case group than in the control group (both p < 0.05). In the case group, the genotype and allele frequencies of the COL2A1 genes, rs1793953 and rs2276454, and Aggrecan VNTR significantly differed in terms of Pfirrmann grades III, IV, and V (all p < 0.05). Personal history of spine sprain or crush injury, history of IVDD in a first-degree relative, and COL2A1 rs2276454 and Aggrecan VNTR presence may be independent risk factors of IVDD (all p < 0.05, odds ratio [OR] >1), whereas tea drinking habit, part-time sports participation, and COL2A1 rs1793953 presence may be protective factors of IVDD (all p < 0.05, OR <1). Our study provides evidence that COL2A1 and Aggrecan genetic polymorphisms may be correlated with the risk and clinicopathological features of IVDD in a Chinese Han population, and ACGL and GTCL haplotypes may be protective factors of IVDD.

The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration

It is well-known that one of the most important features of intervertebral disc degeneration (IDD) is the extracellular matrix (ECM) degradation. Collagen and aggrecan are major components of ECM; the degradation of ECM in intervertebral discs (IVDs) is closely related to the activities of collagenase and aggrecanase. TIMP-3 is the most efficient inhibitor of aggrecanase in IVD. However, only few studies focus on the potential relationship between TIMP-3 and IDD. In our study, we found TIMP-3 gene expression was decreased after stimulating with LPS in rat nucleus pulposus (NP) cells. Then we used a lentivirus vector to reconstruct rat NP cells which high expressed TIMP-3 gene (LV-TIMP3). The upregulation of MMPs and ADAMTSs induced by LPS was significantly inhibited in LV-TIMP3 cells. After overexpression of TIMP-3, the aggrecan breakdown caused by LPS was also reduced in both monolayer culture and three-dimension culture model. To further study the relation between TIMP-3 and IDD, we collected human NP tissue samples of different degenerative degrees. Real-time PCR and immunohistochemical staining showed that the expression of TIMP-3 was negatively correlated with the degree of intervertebral disc degeneration, while MMP-1 and ADAMTS-4 were markedly increased in degenerative IVD. Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD.

ISSLS Prize Winner: Vertebral Endplate (Modic) Change is an Independent Risk Factor for Episodes of Severe and Disabling Low Back Pain.

Longitudinal cohort study of twins representative of the general population. To assess the relationship between Modic change (MC) and severe, disabling low back pain (LBP), features of intervertebral disc degeneration (DD) and incident MC during 10-year follow-up. MC describes vertebral endplate and bone marrow lesions visible on magnetic resonance imaging (MRI). MC has been associated with DD. It remains unclear whether MC causes LBP independently or through association with DD. Moreover, association of MC with severe, disabling LBP is uncertain. Volunteers were recruited from the TwinsUK register to MRI and interview between 1996 and 2000 with a subset attending for follow-up a decade later. MC, DD (evaluated by loss of disc height and signal intensity, presence of disc bulge and anterior osteophytes) and Schmorl's nodes (SN) were determined on T2-weighted lumbar MR scans. Complete data were available for 823 subjects at baseline and 429 at follow-up. Mean age at baseline was 54.0 years (range 32-70) with 96% females. The prevalence of MC was 32.2% at baseline and 48.7% at follow-up. Subjects with MC were older (P < 0.001) and more overweight (BMI: P = 0.026, weight: P < 0.001). At both baseline and follow-up, more subjects reporting severe LBP demonstrated MC (subjects with MC vs. without MC: 35.0% vs. 16.4% respectively, P < 0.001 at baseline; and 35.1% vs. 20.0% respectively, P < 0.001 at follow-up). In multivariable analyses, MC remained significantly associated with episodes of severe, disabling LBP (OR 1.58; 95% CI 1.04-2.41) after adjustment for age, BMI, DD, and SN at baseline. Loss of disc height and disc signal intensity were independently associated with prevalent MC at baseline, and disc height and disc bulge with incident MC during follow-up. MC is an independent risk factor for episodes of severe and disabling LBP in middle-aged women. These observations support further work aimed at identifying the precise histology underlying MC. 2.

Vertebral endplate change as a feature of intervertebral disc degeneration: a heritability study

To study the prevalence of vertebral endplate or Modic change (MC), the progression of MC over a 10-year follow-up and the heritability of MC prevalence in a classical twin study. The study population was recruited from TwinsUK register between 1996 and 2000. MC was evaluated from T2-weighted lumbar magnetic resonance imaging (MRI) at baseline and follow-up. Heritability was estimated using variance components analysis. Baseline MRI with appropriate data was available for 831 twins and follow-up for 436 twins. In total, both baseline and follow-up imaging were available for 347 twins. Mean age of the study population was 54.1 years (range 45.7-62.5) and females comprised 96%. The prevalence of MC at baseline was 32.1% and at follow-up 48.4%. The incidence of MC during the 10-year follow-up was 21.6% and was highest at L4-5 and L5-S1. MC regressed totally in 3.5% of twins. Twins with prevalent MC at baseline demonstrated a higher incidence of MC at upper lumbar levels during follow-up compared to twins without baseline MC (p = 0.009). Probandwise concordance rates were higher in monozygotic (0.56) than dizygotic twin pairs (0.39) suggestive of familial influence. Heritability of MC prevalence was estimated at 30 (16-43) %. The results suggest that MC is generally progressive in middle age and furthermore is heritable. Since MC is associated with disc degeneration, which is also heritable, further work on potential shared mechanisms is needed.

Vertebral Endplate Change as a Feature of Intervertebral Disc Degeneration: A Heritability Study

Introduction Low back pain (LBP) is a common disorder in the western world and accounts for disability and considerable work absenteeism.1 Lumbar disc degeneration (DD) is associated with LBP.2 It has been suggested that different DD phenotypes should be “split” rather than “lumped” into a single phenotype (DD) so as to allow a more meaningful interrogation of the pathogenic processes underlying the constituent traits.3 One trait of special interest is vertebral endplate or Modic change (MC), which comprises vertebral endplate and bone marrow lesions seen on magnetic resonance imaging (MRI).4 This trait has been found to be associated with LBP in some,5 but not all studies.6 MC is classified into three different types: types I-III. Whether MC is entirely environmental in origin, or whether it is influenced by underlying genetic factors, has not been established. Our purpose was to study (1) the prevalence of MC, (2) the progression of MC over a 10-year follow-up, and (3) the heritability of MC prevalence in a classical twin study. Materials and Methods The study population was recruited from TwinsUK register between 1996 and 2000 when the baseline spine MRI study was performed as previously described7 and at follow-up a decade later.3 MC was evaluated from T2-weighted lumbar MRI. Both rostral and caudal endplates of each lumbar segment were coded using the same method at baseline and follow-up.8 The maximum depth and width of each MC was evaluated and the size index was calculated. Heritability was estimated using variance components analysis. MRI with appropriate data was available for 831 twins at baseline and for 436 twins at follow-up. In total, both baseline and follow-up imaging were available for 347 twins. Results Mean age of the study population at baseline was 54.1 years (range, 45.7-62.5) and females comprised 96%. The prevalence of MC at baseline was 32.1% and at follow-up was 48.4%. The incidence of new MC at any level during the 10-year follow-up was 21.6% and was most frequent at L4-L5 and L5-S1. MC regressed totally in 3.5% of twins. The volume of the MC lesions increased during follow-up: the median MC size index summary score was 10.0 (interquartile range = 5.0-18.0) at baseline and 13.5 (interquartile range = 8.0-21.75) at follow-up ( p = 0.012). Twins with prevalent MC at baseline demonstrated a higher incidence of MC at upper lumbar levels compared with twins without baseline MC ( p = 0.015). Probandwise concordance rates were higher in monozygotic (0.56) than dizygotic twin pairs (0.39) suggestive of familial influence. Heritability of MC prevalence was estimated using variance components analysis to be 30 (16-43)%. Conclusion This is the first study to assess the heritability of MC. This study suggests that MC is heritable and progressive in middle age. Further work is needed to define the relationship of MC and lumbar DD. That MC shows a degree of heritability suggests that it is reasonable to search for genetic variants. Disclosure of Interest None declared References Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2197–2223 Livshits G, Popham M, Malkin I, et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 2011;70(10):1740–1745 Williams FM, Popham M, Sambrook PN, Jones AF, Spector TD, MacGregor AJ. Progression of lumbar disc degeneration over a decade: a heritability study. Ann Rheum Dis 2011;70(7):1203–1207 Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 1988;166(1 Pt 1):193–199 Jensen TS, Karppinen J, Sorensen JS, Niinimäki J, Leboeuf-Yde C. Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain. Eur Spine J 2008;17(11):1407–1422 Lim CH, Jee WH, Son BC, Kim DH, Ha KY, Park CK. Discogenic lumbar pain: association with MR imaging and CT discography. Eur J Radiol 2005;54(3):431–437 Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 1999;42(2):366–372 Jensen TS, Sorensen JS, Kjaer P. Intra- and interobserver reproducibility of vertebral endplate signal (modic) changes in the lumbar spine: the Nordic Modic Consensus Group classification. Acta Radiol 2007;48(7):748–754

Distribution and length of osteophytes in the lumbar vertebrae and risk of rupture of abdominal aortic aneurysms: a study of dry bones from Chiang Mai, Thailand.

Vertebral osteophytes are a characteristic feature of intervertebral disc degeneration. In the lumbar spinal region, the two major structures in close proximity anterior to the spine are the inferior vena cava and the abdominal aorta, both of which have been reported to be affected by osteophytes. The purpose of this study was to determine the distribution, classification and lengths of osteophytes in the lumbar vertebrae. One hundred and eighty lumbar columns of 90 males and 90 females from Chiang Mai, Thailand, in the age range 15 to 96 years (mean age, 63 years) were collected. The measuring length of osteophytes was assessed on vertebral body and articular facet. Statistical analysis was performed by descriptive analysis, chi-square and Pearson Correlation. Lumbar osteophytes were presented in 175 specimens (97.2%), 88 males and 87 females. The highest frequency was at L4, most were on the superior, inferior surface of body and articular facet (39.7%, 38.4%, and 22%), respectively. The greatest mean length was 3.47±2.21 mm at L5, and the longest length of anterior superior surface of body was 28.56 mm. The osteophyte length was significantly correlated directly with age (P<0.01), and males were significantly greater than females (P<0.05). The highest prevalence of osteophytes was on the anterior side of superior surface of body (30.4%), and the classification was traction. It can be proposed that the abdominal aorta could be damaged, especially a risk of rupture of abdominal aortic aneurysm.

Features of intervertebral disc degeneration in rat’s aging process

The age-related change is important part of degenerative disc disease. However, no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. 22-month-old Sprague-Dawley (SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types II and X was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto's method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed. There were less collagen type II expression and more collagen type X expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased, compared with that of the young control group (P<0.01). Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types II and X, numbers and areas of afferent vascular buds, the ratio of the non-calcified to the calcified layers, and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.