阻断双侧终板营养途径构建山羊椎间盘退变模型

目的通过建立山羊腰椎双侧终板营养途径阻断的动物模型,观察椎间盘退变(IDD)的情况,研究椎间盘营养途径与IDD的相关性。方法选取8只24月龄雌性关中山羊,每只山羊L2~3、L3~4作为实验椎间盘,麻醉后在平行于终板2 mm的椎体骨质处造成骨缺损,并使用骨水泥填塞,阻断椎体和终板之间的营养通路,L1~2、L4~5作为对照椎间盘。分别于术后4、12、24、48周行X线、MRI检查,各时间点随机处死2只山羊,采集椎间盘标本,计算骨水泥有效阻断面积、椎间高度指数(DHI)和Pfirrmann分级,并行HE、Masson三色、蛋白多糖、番红O染色组织学检查。结果术后骨水泥有效阻断面积达49.6%~69.6%(60.7%±5.3%)。术后48周时实验椎间盘DHI百分比为60.5%~81.7%(72.7%±5.6%),椎间高度丢失较对照差异有统计学意义(P<0.01);术后48周时实验椎间盘Pfirrmann分级为3~5(4.0±0.7)分,较对照差异有统计学意义(P<0.01)。组织学检查证实,实验椎间盘术后12周即发生退变,并随时间(24、48周)逐步加重。结论骨水泥填塞阻断双侧终板营养途径可以构建山羊IDD的动物模型,阻断终板营养途径可以导致IDD发生。     

腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变Pfirrmann分级的相关性

目的 探讨腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变程度之间的关系,为腰椎椎间盘退行性疾病的诊断和治疗提供客观准确的依据。方法 回顾性分析2019年1月—2019年6月来本院就诊的61例腰椎椎间盘退行性变患者临床资料。在腰椎侧位X线片上测量腰椎椎间隙及相应上位椎体的高度,并计算椎间隙高度与上位椎体高度的比值;在腰椎矢状位MRI上评估腰椎椎间盘退行性变Pfirrmann分级;比较不同Pfirrmann分级椎间盘的椎间隙高度与上位椎体高度比值的差异,并采用Spearman相关分析研究椎间隙高度与上位椎体高度比值与相应节段椎间盘Pfirrmann分级之间的相关性。结果 除L₁/L₂节段,其余各节段椎间隙高度与上位椎体高度比值均随着Pfirrmann分级增加而逐渐减小,差异均有统计学意义（P < 0.05）。相同Pfirrmann分级的不同节段椎间盘之间椎间隙高度与上位椎体高度比值差异无统计学意义（P > 0.05）。Spearman相关分析结果显示,L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段Pfirrmann分级与椎间隙高度与上位椎体高度比值呈负相关（r =-0.568,P < 0.05）。结论 临床上测量L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段椎间隙高度与上位椎体高度比值对腰椎椎间盘退行性疾病的诊断可能具有重要意义。     

The effect of disc degeneration on anterior shear translation in the lumbar spine

Many pathologies involving disc degeneration are treated with surgery and spinal implants. It is important to understand how the spine behaves mechanically as a function of disc degeneration. Shear loading is especially relevant in the natural and surgically stabilized lumbar spine. The objective of our study was to determine the effect of disc degeneration on anterior translation of the lumbar spine under shear loading. We tested 30 human cadaveric functional spinal units (L3–4 and L4–5) in anterior shear loading. First, the specimens were imaged in a 1.5 T magnetic resonance scanner. The discs were graded according to the Pfirrmann classification. The specimens were then loaded up to 250 N in anterior shear with an axial compression force of 300 N. Motion of the vertebrae was captured with an optoelectronic camera system. Inter‐ and intra‐observer reliability for disc grading was determined (Cohen's and Fleiss' Kappa), and a non‐parametric test was performed on the translation data to characterize the effect of disc degeneration on this parameter. We found fair to moderate agreement between and within observers for the disc grading. We found no significant effect of disc degeneration on anterior shear translation (Kruskal‐Wallis ANOVA). Our results indicate that disc degeneration, as classified with the Pfirrmann scale, does not predict lumbar spinal motion in shear. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:450–457, 2015.     

Negative effects of ADAMTS‐7 and ADAMTS‐12 on endplate cartilage differentiation

The roles of ADAMTS‐7 and ADAMTS‐12 in disc degeneration have not been previously examined. The purpose of this study was to examine the expression of ADAMTS‐7 and ADAMTS‐12 in the endplate cells isolated from patients with degenerative disc disease and to see whether they are associated with the pathological change of endplate. Sixty‐four degenerated lumbar endplate specimens were obtained from the patients with degenerative disc disease categorized as type Modic I or II in magnetic resonance imaging (MRI) and 12 nondegenerative specimens as control (vertebra burst fracture patients without degenerative change in MRI) during surgical procedures. The expression of ADAMTS‐7 and ADAMTS‐12 was examined by real‐time PCR and Western blotting. A statistically significant increase in mRNA expression of ADAMTS‐7 and ADAMTS‐12 was observed in the endplate cells in degenerative discs compared with nondegenerative discs. The corresponding protein levels of ADAMTS‐7 and ADAMTS‐12 had the same expression patterns. Moreover, ADAMTS‐7 and ADAMTS‐12 down‐regulated the expression of Col II, Sox9, and Col X the marker genes for chondrogenesis. Our results indicate that ADAMTS‐7 and ADAMTS‐12 appear to be potent negative regulators of endplate cartilage development. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1238–1243, 2012     

BNIP3与LC3B在椎间盘退行性变过程中的作用

目的研究BCL2/腺病毒E1B19k Da相互作用蛋白3(BNIP3)基因及微管相关蛋白轻链3B(LC3B)基因在退变椎间盘中的表达情况,探讨其与椎间盘退行性变分级之间的相关性。方法收集2016年4月—2016年7月因腰椎椎间盘突出症于本院接受手术治疗的21例患者的退变腰椎椎间盘标本25个,依据Pfirrmann分级分成5组,分别采用实时荧光定量PCR技术和蛋白质印迹法检测BNIP3、LC3B的m RNA和蛋白表达量,用实时荧光定量PCR技术检测Bcl-2、Bax、Caspase-3的mRNA表达量,并分析BNIP3表达量、LC3B表达量、细胞自噬、细胞凋亡与Pfirrmann分级之间的关系。结果退变椎间盘组织中BNIP3、LC3B在mRNA和蛋白水平的表达均随椎间盘退行性变程度加重而减少。Bcl-2 m RNA的表达随椎间盘退行性变程度加重而减少,Bax与Casepase-3 mRNA的表达随椎间盘退行性变程度加重而增多。结论随着椎间盘退行性变程度的加重,BNIP3与LC3B的表达减少,组织内细胞凋亡水平升高,细胞自噬对组织的保护作用逐渐下降。提示BNIP3与LC3B在腰椎椎间盘退行性变过程中具有重要的调节作用,可能是细胞自噬和凋亡之间的桥梁蛋白。     

腰椎间盘退变性疾患下腰椎终板形态的MRI观察

【摘要】　目的：在MRI片上观察腰椎间盘退变患者下腰椎终板形态的分布规律,分析终板形态和椎间盘退变的关系。方法：回顾分析两组腰椎间盘退变性疾病患者的术前腰椎MRI,A组110例为单节段腰椎间盘突出症患者,B组35例为椎间盘源性腰痛患者。根据正中矢状面MRI T1像,将终板形态分为凹面、平坦、不规则三型;根据Pfirrmann法评定椎间盘退变程度并将Ⅰ～Ⅴ级分别计为1～5分;按Modic改变分级标准判定各节段终板有无Modic改变。分析下腰椎终板的形态特点及三种分型与椎间盘退变程度、Modic改变等的关系。结果：①435个下腰椎节段中,凹面型终板最多（215/435）,A组中占50.6％（167/330）,B组中占45.7％（48/105）,且主要分布于L3/4（108/215）、L4/5（83/215）节段;平坦型终板占29.0％（126/435）,并主要位于L5/S1节段（76/126）;不规则型终板最少（94/435）,A组中占23.0％（76/330）,B组中占17.1％（18/105）,也主要位于L5/S1节段（45/94）。②A组患者中,凹面型终板退变程度平均为3.31±0.81分,平坦型为3.66±0.64分,不规则型为4.16±0.67分,两两比较有显著差异（P＜0.05）;椎间盘突出节段以平坦型（37/110）和不规则型（43/110）终板占多数,无突出节段则以凹面型（137/220）终板占多数,差异有显著性（P＜0.05）;不规则型终板比凹面型和平坦型更容易伴发Modic改变,差异有显著性（P＜0.05）,凹面型和平坦型间无显著性差异（P＞0.05）。③B组患者中,凹面型终板的椎间盘退变程度平均为3.23±0.86分,平坦型为3.54±0.85分,不规则型为3.94±0.54分,仅凹面型和不规则型间差异有显著性（P＜0.05）。④相同终板形态时A组和B组椎间盘退变程度相比均无显著性差异（P＞0.05）。结论：终板形态与椎间盘退变、Modic改变之间有相关性。终板形态由凹面型到平坦型再到不规则型,腰椎间盘退变程度逐渐加重。影像学上终板形态改变在一定程度上反映了椎间盘退变的程度。     

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies

Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used. By the transpedicular approach, a 2 mm tunnel was drilled to the NP through the EP. A partial‐nucleotomy was performed. The tunnel was sealed using a polyurethane scaffold. Lumbar discs were assigned to different groups: L1‐2: nucleotomy; L2‐3: EP tunnel; L3‐4: nucleotomy + EP repair; L4‐5: EP tunnel + repair; L5‐6: control. X‐Ray and MRI were performed at 0, 1, 3, and 6 months after surgery. Disc height and MRI indexes were calculated. Macro‐ and micro‐morphology were analyzed. Pfirrmann and Thompson grades were assigned. The treated discs exhibited a progressive decrease in NP signal intensity and MRI index, displaying specific grades of degeneration based on the surgical treatment. According to Pfirrmann and Thompson grades different procedures were staged as: EP tunnel + repair: grade‐II; EP tunnel: grade‐III, nucleotomy + EP repair: grade‐IV; nucleotomy: grade‐V. A new stepwise model of IDD to study and test safety and efficacy of novel strategies for NP regeneration has been characterized. The different degrees of IDD have been observed similar to Pfirrmann and Thompson grading system. The intact AF allows for loading studies and eliminating the need for AF closure. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2460–2468, 2018.

     

颈椎椎间盘退变对终板结构生物力学特性的影响

目的研究颈椎椎间盘对终板结构生物力学特性的影响。方法50节颈椎标本,采用Nachemson椎间盘分级标准将标本分为4组,正常组(n=22)、Ⅰ度退变组(n=10)、Ⅱ度退变组(n=9)、Ⅲ度退变组(n=9),对每一终板平面上20个特定的测试点进行压缩实验,直径2mm的半球形压头以003mm/s的速度垂直于终板平面下压2mm,由所得的力─位移曲线计算出最大压缩力及刚度,采用单因素方差分析、析因分析、SNK检验及相关分析对实验数据进行统计学分析。结果颈椎椎间盘退变可导致颈椎终板最大压缩力及刚度的显著性减小(P<001),且存在负相关关系(分别为rs=-0429,P<0001;rs=-0244,P<0001);上终板随着椎间盘退变的加重终板平面中央承力逐渐变弱,外周承力逐渐增强,下终板的力学分布无明显改变。结论颈椎椎间盘退变是影响终板结构生物力学特性的重要因素,在进行颈椎前路融合术时应警惕由于椎间盘退变引起的“植入物沉陷”。     

A new quantitative measure of disc degeneration

Background Context

The ability to adequately measure a phenomenon is critical to studying and understanding it. Since 1957, a variety of subjective visual grading methods have been used to assess disc degeneration, but these have been limited by gross ordinal scales and imprecision, as well as suboptimal reliability. Conceptually sound, objective, precise measurements are needed to advance knowledge of disc degeneration and its causes, progression, and consequences.

Expression of Fas receptor and apoptosis in vertebral endplates with degenerative disc diseases categorized as Modic type I or II

Study design

Vertebral endplate tissues were obtained from patients with degenerated lumbar disc classified as Modic type 1 or type 2 and investigated with immunohistochemical staining and the DNA nick end labelling techniques.

Objective

To examine the expression of fas receptor (FasR) and apoptosis in the endplate cells isolated from patients with degenerative disc disease and to see whether they are associated with the pathological change of endplate.

Methods

Fifty-six degenerated lumbar endplate specimens were obtained from the patients with degenerative disc disease categorized as type Modic I or II in magnetic resonance imaging (MRI) and eight nondegenerated specimens as control (vertebra burst fracture patients without degenerative change in MRI) during surgical procedures. Immunohistochemical staining was performed to determine the presence of FasR and apoptosis in sections of those endplate tissues. To investigate whether the FasR expression and apoptosis in endplate were influenced by degeneration and ageing of the discs, the level of FasR expression and apoptosis in the changed and unchanged endplates was analysed.

Results

FasR were expressed in the cytoplasm of the endplate cells. A higher degree of FasR expression and apoptosis in endplate cells in degenerated discs was found than that in nondegenerated discs. In cell culture, the level of FasR expression and apoptosis in cells from the degenerative endplates was higher than those in unchanged endplates. The percentage of FasR-positive endplate and apoptotic endplate cells correlated significantly with the patient's age (r = 0.301, p < 0.05; r = 0.307, p < 0.05. respectively), but not with the degree of disc degeneration in MRI (r = 0.047, p > 0.05; r = 0.066, p > 0.05, respectively).

Conclusion

This is the first study to compare the expression of FasR and apoptosis on vertebral endplate cells in degenerated disc with in nondegenerated disc. The results show that the endplate in degenerated disc may undergo fas-mediated apoptosis and vice versa, endplate degenerative changes may promotes apoptosis of the endplate cells within degenerated disc.     

Structure‐function relationships at the human spinal disc‐vertebra interface

Damage at the intervertebral disc‐vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc‐vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure‐function relationships at this vulnerable location. Vertebra‐disc‐vertebra specimens from human cadaver thoracic spines were scanned with micro‐computed tomography (μCT), surface speckle‐coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy‐one percent of specimens failed initially at the cartilage endplate‐bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc‐vertebra interface injury. The disc‐vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure‐function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc‐vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192–201, 2018.     

The change of whole lumbar segmental motion according to the mobility of degenerated disc in the lower lumbar spine: a kinetic MRI study

Purpose

To analyze the effects of mobility of degenerated disc in the lower lumbar discs (L4–5 and L5–S1) on both whole lumbar motion and adjacent segment ROM.

Methods

The kMRIs with disc degeneration at L4–5 or L5–S1 were classified into three groups: the normal group, the motion-preserved (MP) group and the motion-lost (ML) group based on range of motion (ROM) of 5° in the degenerated segment. Each segmental ROM, whole lumbar motion, and the contribution % of the upper lumbar spine (ULS: L1–2–3) and the lower lumbar spine (LLS: L4–5–S1) motion to whole lumbar motion were measured and compared with each of the other groups.

Results

There were 94, 99 and 66 patients in the normal group, MP group and ML group, respectively. The normal group showed no significant difference compared to the MP group in all ROM parameters. The ML group showed significantly less whole lumbar motion, more contribution % in the ULS and less in the LLS than the normal and the MP groups. The ROM in the superior adjacent segment in the ML group was not significantly different between that in the normal and MP group.

Conclusions

Degenerated lumbar discs did not show hypermobility within functional ROM. Loss of segmental ROM from advanced disc degeneration did not cause an increase in the ROM of the superior adjacent segment in vivo. When the LLS had motion-lost, advanced disc degeneration, whole lumbar motion was significantly decreased and compensatory increase in ROM was accomplished by the ULS.

     

麝香调控退变大鼠颈椎间盘组织基因表达谱的研究

目的　分析麝香对退变椎间盘基因表达谱的调控作用。方法　建立颈椎间盘退变模型。从 9个月模型组、麝香治疗组大鼠颈椎间盘中抽提mRNA ,经反转录分别用Cy3、Cy5荧光标记 ,获得椎间盘cDNA的探针 ;cDNA探针与大鼠BiostarR - 4 0s基因表达谱芯片杂交 ,结果由激光扫描仪扫描并用软件进行图像分析、标准化处理、ratio值分析、聚类分析。结果　麝香组与模型组比较 ,11.1% (共 4 4 1条 )基因表达发生明显变化 ,其中 2 6 0条基因表达量上升(R >2 .0 ) ,182条基因表达量明显下降 (R <0 .5 )。经过信息学分析 ,在上述两张芯片上都有基因表达量明显变化的 90条 (R >2 .0或 <0 .5 ) ,其中基因表达量都明显上调的 2 5条 (R >2 .0 ) ,其中功能明确的基因有 3条 ;都明显下调的 2 0条 (R <0 .5 ) ,其中功能明确的基因有 5条 ;麝香发挥明显上调作用的共 13条 (由R <0 .5到R >2 .0 )。结论　麝香对退变椎间盘出现总体调控。筛选出大鼠退变椎间盘中相关基因 ,特别是有较多的细胞信号和传递蛋白类基因表达 ,说明细胞内外的信号传导介导了椎间盘退变过程。     

Simulation of biological therapies for degenerated intervertebral discs

The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three‐dimensional finite element model based on a cell‐activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies‐increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)‐to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long‐term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:699–708, 2016.     

Disc degeneration contributes to the denser bone in the subendplate but not in the vertebral body in patients with lumbar spinal stenosis or disc herniation

BACKGROUND CONTEXTIt is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone.PURPOSETo evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate.STUDY DESIGN/SETTINGA single-center, retrospective cohort study.PATIENT SAMPLEA total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data.OUTCOME MEASURESThe vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well.METHODSThe age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ.RESULTSThis study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ.CONCLUSIONSDisc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.     

Microcalcification of lumbar spine intervertebral discs and facet joints is associated with cartilage degeneration,but differs in prevalence and its relation to age

Cartilage calcification (CC) is associated with degeneration in non‐vertebral joints, but little is known about CC and lumbar vertebral joints. The goal of this study was to analyze the prevalence of CC in lumbar facet joints (FJ) and intervertebral discs (IVD) and its relation to cartilage degeneration and age in a non‐selected cohort of the general population. The segment L4/5 of 85 consecutive donors (mean age 61.9 years) was analyzed by high‐resolution imaging digital‐contact radiography (DCR). Quantification was achieved by measuring CC in % of total cartilage area. Histological degeneration of FJs and IVDs was determined by OARSI and Boos scores. Prevalence of CC was 36.5% for FJ (95%CI (0.26, 0.48)) and 100% for IVD (95%CI (0.96, 1.00)). The amount of IVD CC (3.36% SD ± 7.14) was 16.3 times higher (p < 0.001) than that of the FJ (0.23% SD ± 0.53) and independent of each other (p = 0.07). The amount of FJ CC correlated significantly with FJ and IVD degeneration (FJ r = 0.44, p = 0.01, IVD r = 0.49, p = 0.006) while the amount of IVD CC correlated only with IVD degeneration (r = 0.54, p < 0.001). Age correlated with IVD CC (r _s = 0.35, p < 0.001), but not FJ CC (r _s = 0.04, p = 0.85). We conclude that IVD fibrocartilage is particularly prone to calcification. A causal relationship between lumbar CC and degeneration is possible, but the clear differences in IVD fibrocartilage CC and FJ synovial joint CC in regard to prevalence and in relation to age point to a differential role of CC in single compartments of the respective motion segment in lumbar spine degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2692–2699, 2017.

     

Association of the Tag SNPs in the Human SKT Gene (KIAA1217) With Lumbar Disc Herniation

Lumbar disc herniation (LDH) is one of the most common musculo‐skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA1217 (alias SKT, the human homolog of murine Skt [Sickle tail]) is a good candidate for an LDH susceptibility gene because SKT is specifically expressed in nucleus pulposa of intervertebral discs (IVDs) in humans and mice, and Skt^Gt mice, which are established through a large‐scale gene‐trap mutagenesis, exhibit progressive, postnatal onset abnormality of the IVDs. Here, we report the association of SKT with LDH. Using tag SNPs, we examined the association in two independent Japanese case‐control populations and found a significant association with SKT rs16924573 in the allele frequency model (p = 0.0015). The association was replicated in a Finnish case‐control population (p = 0.026). The combined p value of the two population by meta‐analysis is 0.00040 (OR, 1.34; 95% CI, 1.14–1.58). Our data indicate that SKT is involved in the etiology of LDH.     

Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post‐operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze‐drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC‐injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10–12%) viscoelastic moduli after mild degeneration within goats, though the inter‐animal differences were relatively large (complex modulus ～12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ～75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 703–709, 2013     

Age-dependent correlation of low-back pain and lumbar disc degeneration

The prevalence of lumbar disc degeneration in subjects suffering from low-back pain (n = 207; age range 10–49 years) and in age-matched asymptomatic controls (n = 216) was investigated by magnetic resonance imaging. The percentage of subjects with degenerated discs increased with age; starting from the age of 15 years, this increase was more rapid in subjects with low-back pain. Concurrently, the number of degenerated discs was higher in the pain group than in controls. Lumbar disc degeneration manifests earlier and in a greater percentage of subjects with low-back pain than in asymptomatic controls.