Severity Of Disc Degeneration Research Articles

Association between chronic inflammation and latent infection of Propionibacterium acnes in non-pyogenic degenerated intervertebral discs: a pilot study.

Propionibacterium acnes may be considered a new pathogeny for disc degeneration, but its pathological role has remained unclear. This study was designed to determine whether the latent infection of P. acnes was associated with chronic inflammation in degenerated intervertebral discs via quantification of the levels of a series of cytokines and neutrophils. Here, 76 degenerated intervertebral discs were harvested from patients with lower back pain and/or sciatica. Discs with and without P. acnes infection were distinguished and identified using anaerobic culture combined with 16S rDNA PCR and histological examination. Then, cytokines of TNF-α, IL-1β, IL-6, IL-8, MCP-1, MIP-1α, and IP-10, and the numbers of neutrophils were quantified and compared. The severity of disc degeneration and the prevalence of Modic changes were also evaluated between discs with and without P. acnes. After anaerobic culture and PCR examination, 15 intervertebral discs were placed in the P. acnes-positive group. Another 15 discs were selected from the remaining bacteria-free samples and formed a matched P. acnes-negative group. IL-8, MIP-1α, MCP-1, IP-10, TNF-α, and neutrophils were much higher in P. acnes-positive group than that in the matched P. acnes-negative group. However, only IL-8, MIP-1α, and neutrophils were statistically significant. Furthermore, 7 of 15 P. acnes-positive samples were histologically positive and a subgroup analysis suggested that both histological and PCR-positive samples had the highest concentrations of cytokines of IL-8, MIP-1α, TNF-α, and MCP-1 and the greatest numbers of neutrophils. PCR-positive but histologically negative samples showed the second-greatest, and matched P. acnes-negative samples showed the fewest. However, the difference was only statistically significant between samples found positive under both histology and PCR and samples found negative for P. acnes. Finally, P. acnes-positive group had significantly lower height of intervertebral discs and there was a trend with higher proportion of Modic changes in P. acnes-positive group, but without statistical results. Latent P. acnes infection was associated with chronic inflammation in degenerated intervertebral discs, especially in the samples with visible bacteria in histology, which manifested as increased numbers of cytokines and neutrophils. Discs with P. acnes infection had much severer disc degeneration and P. acnes-associated chronic inflammation may be the reason.

Dynamic foraminal dimensions during neck extension and rotation in fusion and artificial disc replacement: an observational study

BackgroundChanges in the dimensions of the cervical neural foramina (CNF) are considered to be a key factor in nerve root compression and development of cervical radiculopathy. However, to what extent foraminal geometry differs between patients who underwent anterior cervical discectomy and fusion (ACDF) and those who underwent total disc arthroplasty with an artificial disc (AD) during physiological motion is largely unknown. PurposeThe objective of this study is to compare CNF dimensions during physiological neck motion between ACDF and AD. Study Design/SettingThis is a retrospective comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution. Patient SampleA total of 16 single-level C5–C6 ACDF (4 males, 12 females; 28–71 years) and 7 single-level C5–C6 cervical arthroplasty patients (3 males, 4 females; 38–57 years), at least 12 months after surgery (23.6±6.8 months) were included. Outcome MeasuresPatient demographics, preoperative magnetic resonance imaging (MRI)-based measurements of cervical spine degeneration, and 2-year postoperative measurements of dynamic foraminal geometry were the outcome measures. MethodsBiplane X-ray images were acquired during axial neck rotation and neck extension. A computed tomography scan was also acquired from C3 to the first thoracic vertebrae. The subaxial cervical vertebrae (C3–C7) were reconstructed into three-dimensional (3D) bone models for use with model-based tracking. Foraminal height (FH) was calculated as the 3D distance between the superior point of the inferior pedicle and the inferior point of the superior pedicle using custom software. Foraminal width (FW) was similarly calculated as the 3D distance between the anterolateral aspect of the superior vertebral body inferior notch and the posterolateral aspect of the inferior vertebral body superior notch. Dynamic foraminal dimensions were quantified as the minimum (FH.Min, FW.Min), the range (FH.Range, FW.Range), and the median (FH.Med, FW.Med) of each trial and then averaged over trials. Mixed model analysis of variance framework was used to examine the differences between ACDF and AD groups. The initial severity of disc degeneration as determined from preoperative MRI images was introduced as covariates in the models. ResultsAt the operated level (C5–C6), FH.Med and FH.Range were smaller in ACDF than in AD during axial rotation and neck extension (p<.003 to p<.05). At the superior adjacent level (C4–C5), no significant difference was found. At the inferior adjacent level (C6–C7), FW.Range was greater in ACDF than in AD during axial rotation and extension (p<.05). At the non-adjacent level (C3–C4), FW.Range was greater in ACDF than in AD during extension (p<.008). ConclusionsThis study demonstrated decreases in foraminal dimensions and their range for ACDF compared with AD at the operated level. In contrast, it demonstrated increases in the range of foraminal dimensions during motion for ACDF compared with AD at the non-operated segments. Together, these data support the notion that increased mobility at the non-operated segments after ACDF may contribute to a greater risk for adjacent segment degeneration. Because of the significant presence of range variables in the findings, the current data also indicate that a dynamic evaluation is likely more appropriate for evaluation of the differences in foramina between ACDF and AD than a static evaluation.

Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain.

IntroductionDisc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.ObjectivesThis study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation.MethodsA descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis.ResultsMean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis.ConclusionsSNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.

Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model.

The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224-232, 2018.

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid.

CSF was examined for differential protein expression in healthy control participants, pain-free adults with asymptomatic intervertebral DD, and LBP patients with painful intervertebral DD. While DD was related to inflammation regardless of pain status, painful degeneration was associated with markers linked to nerve injury.

Relationship between disc degeneration and facet joint arthrosis-a MRI study

IntroductionSpinal degeneration includes degenerative changes occurring in the anteriorly located fibro-cartilaginous intervertebral discs and posteriorly placed synovial facet joints. The stability of each spinal motion segment is dependent on both these components. Thus an MRI based study on low back pain subjects was undertaken to assess the association between disc degeneration (DD) and facet joint arthrosis (FJA). Materials & methodThe study was conducted on 50 low back patients selected on the basis of predefined questionnaire and taken up for MRI assessment for grading disc degeneration and facet joint arthrosis. The severity of DD and FJA was evaluated at each motion segment and assessed with respect to gender, spinal level and the interdependence of disc and facet joint degeneration was defined. ResultsThe degeneration process at the disc and facet joint was independent of gender (p>0.05) but dependent on the spinal level (p<0.05). Disc degeneration was seen at the caudal most level while facet joint degeneration was seen in the L4–L5 spinal level. FJA was evident even without evidences of disc degeneration and no significant association was observed between discs and the facet joints. DiscussionThe role of small facet joints should not be overlooked while defining low back pain etiology as these joints play a significant role in load transmission and rotational kinematics. This knowledge can be of help in defining appropriate treatment modality for better patient care.

Lumbar disc degeneration is an equally important risk factor as lumbar fusion for causing adjacent segment disc disease

Treatment of degenerative spinal disorders by fusion produces abnormal mechanical conditions at mobile segments above or below the site of spinal disorders and is clinically referred to as adjacent segments disc disease (ASDD) or transition syndrome in the case of a previous surgical treatment. The aim of the current study is to understand with the help of poro-elastic finite element models how single or two level degeneration of lower lumbar levels influences motions at adjacent levels and compare the findings to motions produced by single or two level fusions when the adjacent disk has varying degree of degeneration. Validated grade-specific finite element models including varying grades of disc degeneration at lower lumbar levels with and without fusion were developed and used to determine motions at all levels of the lumbar spine due to applied moment loads. Results showed that adjacent disc motions do depend on severity of disc degeneration, number of disc degenerated or fused, and level at which degeneration or fusion occurred. Furthermore, single level degeneration and single level fusion produced similar amount of adjacent disc motions. The pattern of increase in adjacent segment motions due to disc degeneration and increase in motions at segment adjacent to fusion was similar. Based on the current study, it can be concluded that disc degeneration should also be considered as a risk factor in addition to fusion for generating adjacent disc degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:123-130, 2017.

Matrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers

Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. Transcriptional expression of fibrosis markers (COL1A1, COL3A1, FN1, HSP47, MMP12, RASAL1) were analyzed in degenerated (D) and non-degenerated (ND) human nucleus pulposus (NP) and annulus fibrosus (AF) cells, along with traditional (SOX9, ACAN) and newly established degeneration markers (CDH2, KRT19, KRT18, FBLN1, MGP, and COMP). Protein expression was investigated by immunohistochemistry in human IVDs, and in rodent IVDs undergoing natural ageing or puncture-induced degeneration. Co-expression with myofibroblast markers was examined by double staining on human and rat specimens. Disc degeneration severity and extent of fibrosis were determined by histological scoring and picrosirius red staining respectively. Human D-NP showed more intensive staining for picrosirius red than ND-NP. Among the genes examined, D-NP showed significantly higher MMP12 expression along with lower KRT19 expression. Protein expression analysis revealed increased MMP12(+) cells in human D-IVD. Histological scoring indicated mild degeneration in the punctured rat discs and discs of ageing mouse. Higher MMP12 positivity was found in peripheral NP and AF of the degenerative rat discs and in NP of the aged mice. In addition, human D-NP and D-AF showed increased α-SMA(+) cells, indicating enhanced myofibroblast activity. MMP12 was found co-expressed with α-SMA, FSP1 and FAP-α in human and rat degenerative IVDs. Our study suggests that in addition to a reduced KRT19 expression, an increased expression of MMP12, a profibrotic mediator, is characteristic of disc degenerative changes. Co-expression study indicates an association of the increased MMP12 positivity with myofibroblast activity in degenerated IVDs. Overall, our findings implicate an impact of MMP12 in disc cell homeostasis. The precise role of MMP12 in IVD degeneration warrants further investigation.

Classification of Schmorl's nodes of the lumbar spine and association with disc degeneration: a large-scale population-based MRI study

Schmorl's nodes (SN) are highly associated with lumbar disc degeneration (DD). However, SN present with different morphologies/topographies that may be associated with varying degrees of DD. This study proposed a classification of SN to determine their morphological/topographical prevalence and association with the severity of DD. Sagittal T2-weighted MRIs were assessed to identify SN and additional imaging findings from L1-S1 in 2,449 individuals. SN characteristics were classified by six criteria: disc level; endplate involvement; shape; size; location of endplate zone; and the presence of marrow changes. Hierarchical clustering was performed to identify distinct SN characteristics with endplate patterns. Good to excellent observer classification reliability was noted. SN most commonly presented at the L1 and L2 disc levels, and entailed one-third of the endplate, predominantly the middle zone. Round shape (39.2%) was the most common SN shape. Four specific SN and endplate linkage patterns were identified. 8.3% of identified SN (n=960) were "Atypical SN". Multivariable regression showed that "Typical SN" and "Atypical SN", depending on levels, were associated with an adjusted 2- to 4-fold and a 5- to 13-fold higher risk of increased severity of DD, respectively (p<0.05). This is the first large-scale magnetic resonance imaging (MRI) study to propose a novel SN classification. Specific SN-types were identified, which were associated with more severe DD. This study further broadens our understanding of the role of SN and degrees of DD, further expanding on the SN phenotyping that can be internationally adopted for utility assessment.

Systemic blood plasma CCL5 and CXCL6: Potential biomarkers for human lumbar disc degeneration.

Lumbar disc degeneration severity on magnetic resonance imaging (MRI) is associated with low back pain. Pro-inflammatory chemokines CCL5 and CXCL6 are released by induced degenerative discs, and CCL5 has been associated with discogenic back pain. A case-control study was performed, based on the Hong Kong Disc Degeneration Population-Based Cohort of Southern Chinese, to investigate if systemic levels of CCL5 and CXCL6 were elevated in subjects with disc degeneration compared to non-degenerated individuals. Eighty subjects were selected, 40 with no disc degeneration (control group; DDD score 0) and 40 with moderate/severe disc degeneration (disc degeneration group; DDD score ≥5) as noted on MRI. Subjects were matched for age, sex, body mass index and workload. Blood plasma samples were obtained from each individual, and levels of CCL5 and CXCL6 were measured. Secondary phenotypes of lumbar disc displacement and cervical disc changes were also assessed. CCL5 concentrations were significantly increased in the disc degeneration (mean: 19.8 ng/mL) compared to the control group (mean: 12.8 ng/mL) (p = 0.015). The degeneration group demonstrated higher levels of CXCL6 (mean: 56.9 pg/mL) compared to the control group (mean: 43.4 pg/mL) (p = 0.010). There was a trend towards elevated CCL5 levels with disc displacement in the degeneration group (p = 0.073). Cervical disc degeneration was not associated with elevated chemokine levels (p > 0.05). This is the first study to note that elevated systemic CCL5 and CXCL6 were associated with moderate/severe lumbar disc degeneration, further corroborating tissue studies of painful discs. These chemokines may be systemic biomarkers for the diagnosis and monitoring of disc degeneration.

Age-Related Incidence of Cervical Spondylosis in Residents of Jeju Island.

Study DesignCervical spine radiograms of 460 Jeju islanders.PurposeTo investigate the age-matched incidences and severity of the cervical disc degeneration and associated pathologic findings.Overview of LiteratureSeveral related studies on the incidences of disc and Luschka's and facet joint degeneration have provided some basic data for clinicians.MethodsCervical radiographs of 460 (220 males and 240 females) patients in their fourth to ninth decade were analyzed. Ninety patients in their third decade were excluded because of absence of spondylotic findings.ResultsOverall incidence of cervical spondylosis was 47.8% (220 of 460 patients). The percentile incidences of spondylosis in the fourth, fifth, sixth, seventh, eighth and ninth decade was 13.2% (10 of 76 patients), 34.6% (37 of 107 patients), 58.9% (66 of 112 patients), 58.8% (50 of 85 patients), 70.3% (45 of 64 patients) and 75.0% (12 of 16 patients), respectively. The percentile incidences of one, two, three, four and five level spondylosis among 220 spondylosis patients was 45.5% (n=100), 34.1% (n=75), 15.0% (n=33), 4.5% (n=10), and 0.9% (n=2). Severity of disc degeneration ranged from ± to ++++, and was ± in 6.0% (24 segments), + in 49.6% (198 segments), ++ in 35.3% (141 segments), +++ in 9.0% (36 segments) and ++++ in 0.25% (one segment). Spurs and anterior ligament ossicle formed at the spondylotic segments, mostly at C4~6. The rate of posterior corporal spurs formation was very low. Olisthesis and ossification of the posterior longitudinal ligament were rarely combined with spondylosis. Cervical lordotic curve decreased gradually according to the progress of severity of spondylosis.ConclusionsThe incidence of cervical spondylosis and number of spondylotic segments increase, and degeneration gradually becomes more severe with age.

Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP) tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E₂) in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10^-5, 10^-7 and 10^-9 M) or without (control) E2 for48 hours. The estrogen receptor (ER)-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG) content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

A Dose-response relationship between severity of disc degeneration and intervertebral disc height in the lumbosacral spine.

IntroductionVaried definitions of disc pathology exist in the literature. Magnetic Resonance Imaging (MRI) classification systems incorporate several qualitative features including disc appearance, the distinction between the nucleus and the annulus, signal intensity and intervertebral disc height. The lack of a continuous measure has made it difficult to sensitively examine degenerative disc disease. This study sought to examine the relationship between disc degeneration and intervertebral disc height.Methods72 community-based individuals not selected for low back pain had MRI from which the presence of lumbosacral disc degeneration was identified using the Pfirrmann grading system, and intervertebral disc height was measured.ResultsAt each lumbosacral level, with higher grade of disc degeneration, intervertebral disc height was reduced (all p ≤ 0.003). Results remained unchanged when grade 5 disc degeneration, which necessitated a collapsed disc space, was excluded from analyses (all p ≤ 0.03). To quantify these associations, at each lumbosacral level, for every grade increase in disc degeneration, there was a reduction in intervertebral disc height, after adjusting for age, gender, Body mass index and smoking history (β range from −0.98 mm to −1.60 mm, 95 % CI range from −2.37 to −0.31, all p ≤ 0.005).ConclusionThis study has demonstrated a negative dose–response relationship between increasing severity of disc degeneration with a reduction in intervertebral disc height. Although the assessment of disc degeneration incorporates a number of qualitative measures, these data substantiate the utility of intervertebral disc height as a quantitative and continuous outcome measure in epidemiological studies, and potentially clinical practice.

Association of collagen I, IX and vitamin D receptor gene polymorphisms with radiological severity of intervertebral disc degeneration in Southern European Ancestor.

Several genomic loci have been previously found to be associated with intervertebral disc degeneration, so far. Data are mostly derived from northern European countries whereas data derived from Southern European Ancestor are limited. This study aimed to evaluate the association between radiological disease severity of lumbar disc degeneration and certain genetic loci in a sample of participants from Southern Europe. Seventy-five patients with mild to severe lumbar disc degeneration and 25 healthy controls were enrolled into the study. In each subject, each lumbar intervertebral disc was separately examined to obtain a total radiological score for disease severity. In addition, single-nucleotide polymorphisms of predefined genetic samples were analyzed in all participants: COL1A1 Sp1, COL9a2 Trp2, COL9a3 Trp3, and VDR TaqI. Degeneration scores were significantly worse in cases with COL1A1 Sp1, COL9a3 Trp3, and VDR TaqI mutations; however, COL9a2 Trp2 mutation was not associated with a difference in the severity of disc degeneration. In addition, subjects with mutation in more than one gene sample (n = 20) had significantly worse degeneration scores than the remaining study participants (n = 80) (17.70 ± 2.72 vs. 21.81 ± 1.81, p < 0.001). Single-nucleotide polymorphisms occurring in COL1A1, COL9a3 and VDR genes seem to be associated with the development of lumbar disc degeneration in this cohort, possibly with even more pronounced association when multiple mutations are present in the same individual. By further prospective twin studies in associated genes and analyses of their relationship with environmental factors in an internationally sampled large cohort will make a more clear-minded conclusion about their association with disc degeneration, which would yield better appreciation and clinical planning of some predisposed people for these pathologies.

Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model

Background ContextChronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood.In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo. PurposeThe goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain. Study DesignThis study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration. MethodsSPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or mechanical stimuli on the hindpaw (acetone and von Frey tests), and latency to fall in the rotarod assay, respectively. ResultsThe SPARC-null mice exhibited decreased tolerance to axial stretching, hindpaw cold hypersensitivity, and motor impairment compared with age-matched control mice. The severity of disc degeneration increased with age in both SPARC-null and control mice and by 78 weeks of age, the same proportion of lumbar discs were abnormal in SPARC-null and control mice. However, the degree of degeneration was more severe in the SPARC-null mice. In both SPARC-null and control mice, tolerance to axial stretching but not hindpaw cold sensitivity correlated with disc degeneration severity. Motor impairment correlated with degeneration severity in the SPARC-null mice only. ConclusionsThese data suggest that internal disc disruption contributes to axial low back pain and motor impairment but not to radiating leg pain. These results have implications for the optimization of mechanism-based treatments strategies.

Evaluation of 12 Novel Molecular Markers for Degenerated Nucleus Pulposus in a Chinese Population.

A transcriptional expression assessment of human samples. To evaluate 12 new candidate nucleus pulposus (NP) markers in degenerative disc disease in a Chinese population. Disc degeneration is a major contributor of low back pain. However, no specific and reliable markers of degeneration of NP are available. Specimens of NP were collected from 81 patients and grouped into the degenerated disc group (undergoing discectomy and fusion with significant signs of disc degeneration) and the trauma control group (undergoing anterior vertebral body and disc excision and fusion without signs of disc degeneration). Lumbar spine magnetic resonance imaging, hematoxylin-eosin staining, and safranin O staining of sections of NP tissues were conducted to evaluate the severity of the disc degeneration in all samples. Quantitative reverse transcription polymerase chain reaction was performed to investigate the levels of mRNA expression of these genes, as well as those of aggrecan, type II collagen, and SRY-box 9 (SOX-9). Degenerated samples were also divided into groups according to Pfirrmann grading system to elucidate the association of severity of degeneration and gene transcriptional levels. We also tested the relationship between mRNA levels of these genes and clinical characteristics such as hypertension and diabetes mellitus. We demonstrated that 11 of the 12 candidates showed significant differential expression in degenerated discs. Changes in the expression of these 11 genes were determined to be risk factors in degenerative disc diseases. The expression of neurochondrin (NCDN), keratin 8 (KRT8), and matrix Gla protein (MGP) even showed significant changes among subgroups of patients with degenerative disc disease stratified according to the Pfirrmann grading system. The expression of keratin 18 (KRT18), cadherin 2 (CDH2), synaptosomal-associated protein 25 (SNAP25), KRT8, and NCDN was significantly decreased in patients with hypertension. In contrast, the expression of MGP and cartilage oligomeric matrix protein was significantly upregulated in patients with diabetes mellitus. Overall, we demonstrated the clinical utility of 11 novel NP markers for degenerative disc disease. Among them, the expression of NCDN, KRT8, and MGP may indicate the severity of disc degeneration. N/A.

Assessment of functional and behavioral changes sensitive to painful disc degeneration.

The development of an in vivo rodent discogenic pain model can provide insight into mechanisms for painful disc degeneration. Painful disc degeneration in rodents can be inferred by examining responses to external stimuli, observing pain-related behaviors, and measuring functional performance. This study compared the sensitivity of multiple pain and functional assessment methods to disc disruption for identifying the parameters sensitive to painful disc degeneration in rats. Disc degeneration was induced in rats by annular injury with saline injection. The severity of disc degeneration, pain sensitivity, and functional performance were compared to sham and naïve control rats. Saline injection induced disc degeneration with decreased disc height and MRI signal intensity as well as more fibrous nucleus pulposus, disorganized annular lamellae and decreased proteoglycan. Rats also demonstrated increased painful behaviors including decreased hindpaw mechanical and thermal sensitivities, increased grooming, and altered gait patterns with hindpaw mechanical hyperalgesia and duration of grooming tests being most sensitive. This is the first study to compare sensitivities of different pain assessment methods in an in vivo rat model of disc degeneration. Hindpaw mechanical sensitivity and duration of grooming were the most sensitive parameters to surgically induced degenerative changes and overall results were suggestive of disc degeneration associated pain.

The effect of bone morphogenetic protein-2 injection at different time points on intervertebral disk degeneration in a rat tail model.

Prospective in vivo rat tail model of disk degeneration comparing the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) injection over various time points and grades of degeneration. To evaluate the effect of timing and disk grade on rhBMP-2 injection in a rat tail model of disk degeneration. rhBMP-2 stimulates the proliferation of intervertebral disk cells and the secretion of extracellular matrix. However, few in vivo studies have demonstrated whether rhBMP-2 also improves disk degeneration and the severity of disk degeneration beyond which disks cannot be recovered by rhBMP-2 treatment. Two coccygeal disks of each rodent subject were punctured percutaneously using an 18 G needle. At 4 weeks after the puncture, disks demonstrating induced degeneration were divided into 3 groups. Groups 1, 2, and 3 were treated with 7.5 μg rhBMP-2 or phosphate buffered saline by injection into the disk at 4, 6, and 8 weeks postpuncture, respectively. Plain radiographs and magnetic resonance images (MRIs) were obtained on the day of puncture and every 2 weeks thereafter until sacrifice. At 6 weeks after injection, each group was killed and examined with histologic and immunohistochemical analysis. According to MRI disk grade evaluation of the degenerative disk, rhBMP-2 significantly improved degeneration grade in group 1 at 2 weeks after injection. According to radiographic disk height index, groups 1 and 2 showed a trend toward improvement at 2 weeks after rhBMP-2 injection. Chondrogenic differentiation was noted on immunohistochemical staining of many disks treated with rhBMP-2. rhBMP-2 injection of degenerated disks at 4 weeks postpuncture induced a transient improvement in disk grade on MRI and stimulated chondrogenic differentiation. These data suggest rhBMP-2 as a potential therapy for degenerative disk disease.

Age-Related Incidences of Spondylosis of the Lower Cervical Spine Radiographic Study of 460 Jeju Islanders

Study design: Cervical spine radiograms of 460 Jeju islanders, taken at the Cheju Halla General Hospital, Jeju, were the study materials. Objectives: To investigate the age-matched incidences and severity of the cervical disc degeneration and associated pathologic findings. Summary of background data: There exist several previous studies on the incidences of disc and Luschka’s and facet joint degeneration in the Europeans and Asians which provided the basic data for the interested clinicians. Methods: Cervical radiographs of 460 (220 males and 240 females) patients of fourth to ninth decade were subjected to this prospective study. Ninety patients of third decade were excluded because none showed the spondylotic findings on radiograms. There were 76 patients (16.5%) in fourth decade, 107 patients (23.3%) in fifth decade, 112 patients (24.3%) in sixth decade, 85 patients (18.5%) in seventh decade, 64 patients (13.9%) in eighth decade, and 16 patients (3.5%) in ninth decade. Results: Overall incidences of cervical spondylosis were 47.8% (220 patients out of 460 patients). The percentile incidences of spondylosis in fourth, fifth, sixth, seventh, eighth and ninth decade were 13.2%(10 out of 76 patients), 34.6%(37 out of 107 patients), 58.9%(66 out of 112 patients), 58.8%(50 out of 85 patients), 70.3% (45 out of 64 patients), and 75.0%(12 out of 16 patients). The percentile incidences of one, two, three, four and five level spondylosis among 220 spondylosis patients were 45.5%(100 patients), 34.1%(75 patients), 15.0%(33 patients), 4.5%(10 patients), and 0.9%(2 patients). Severity of disc degeneration ranged from ± to ++++; ± in 6.0% (24 segments), + in 49.6% (198 segments), ++ in 35.3% (141 segments), +++ in 9.0% (36 segments) and ++++ in 0.25% (1 segment). Spurs and anterior ligament ossicle formed at the spondylotic segments, mostly at C4~6. Posterior corporal spurs formed in quite low rates. Olisthesis and OPLL rarely combined with spondylosis. Cervical sagittal lordotic curve decreased gradually according to the progress of spondylosis, particularly over + disc degeneration. Conclusion: It was evidently shown that the incidences of cervical spondylosis and numbers of spondylotic segments increased, and that degeneration became more severe gradually throughout the aging process.

Surgical treatment for cervical spondylotic myelopathy with different characteristics in imaging examinations

Objective To investigate the clinical features, operation procedures and clinical outcomes of cervical spondy-lotic myelopathy with different imageological characteristics. Methods Two hundred and twenty one cervical myelopathy with different imageological characteristics patients between November 2011 and October 2013 were involved in this retrospective study. Patients were distributed into three groups, namely mild group （A）, moderate group （B） and severe group（C）, based on severi-ty of complexity by imageological variables （severity of cervical spine degeneration, the number of spinal cord compression, severi-ty of spinal cord compression and difficulty in operation）. Preoperative and postoperative Japanese Orthopaedic Association （JOA） score and mean recovery rate were collected to evaluate the postoperative clinical effects. Demographic data and imageological characteristics were recorded;Univariate analysis or analysis of variance was conducted to analyze the correlation between post-operative JOA recovery rate with gender, age, course of disease, severity of spinal cord compression, the number of segment with spinal cord compression, severity of disc degeneration, MRI T2 increased signal intensity, cervical instability, cervical kyphosis, developmental cervical spinal stenosis and ossification of posterior longitudinal ligament. Results There was no significant differ-ence in gender between three groups. There was significant difference in age, preoperative JOA score and improvement rate be-tween group A and group B （C）. All patients received decompression and reconstruction by anterior or posterior approach. The ra-tio of anterior approach in group A, B and C was 91.1%（72/79）, 79.8%（71/89）, 35.8%（18/53）. The last follow-up JOA recovery rate of group A, B and C was 75.4%±6.4%、67.7%±8.7%、62.8%±10.4%. The last follow-up JOA recovery rate was correlated with duration of disease, the number of spinal cord compression and severity of spinal cord compression. Age, duration of course, preop-erative JOA score, degree of cord compression, the number of segment with cord compression, degree of disc degeneration, MRI T 2 increased signal intensity, cervical instability, cervical kyphosis, developmental cervical spinal stenosis and OPLL. Conclusion Patients suffering from cervical myelopathy with different imageological have good prognosis by appropriate operation procedure. Key words: Cervical spondylosis Magnetic resonance imaging Surgical procedures; operative