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.     

Alterations in intervertebral disc composition,matrix homeostasis and biomechanical behavior in the UCD‐T2DM rat model of type 2 diabetes

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738–746, 2015.     

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.     

Alterations of ADAMTSs and TIMP‐3 in human nucleus pulposus cells subjected to compressive load: Implications in the pathogenesis of human intervertebral disc degeneration

Intervertebral disc degeneration (IDD) pertains to the loss of extracellular matrix (ECM), particularly the early loss of aggrecan, the turnover of which is regulated by ADAMTSs. Amongst the etiological factors of IDD, mechanical stress plays an important role in the physiological and pathological processes of nucleus pulposus (NP) cells. However, the role of ADAMTSs and their inhibitor in human NP cells under mechanical stress has not been elucidated to date. The purpose of this study was to investigate the role of ADAMTSs and TIMP‐3 in NP cells under mechanical stress. Human NP cells isolated from non‐degenerative and degenerative discs were subjected to dynamic compressive load. The expression of ADAMTSs, aggrecan, and TIMP‐3 was detected by quantitative real‐time PCR and/or Western blot. Consequently, the gene expression of ADAMTS‐1, 4, and 5 increased significantly in loaded NP cells compared with not‐loaded cells from either non‐degenerative or degenerative discs, whereas the gene expression of aggrecan decreased significantly. Moreover, Western blot indicated increased protein levels of ADAMTSs‐1, 4, and 5. However, the expression of TIMP‐3 altered insignificantly. Together, this study is the first addressing the underlying mechanisms of compressive load as a contributing factor to IDD in terms of ADAMTSs. Our results suggest that compressive load leads to the increase in ADAMTS‐1, 4, and 5 that contributes to the decrease of aggrecan and IDD via TIMP‐3 independent machinery. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:267–273, 2012     

Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system

BACKGROUND CONTEXTBack and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.PURPOSETo quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.STUDY DESIGNAn immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.METHODSHuman IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.RESULTSFifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).CONCLUSIONSBMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.CLINICAL SIGNIFICANCEBMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.     

Asymmetry between the superior and inferior endplates is a risk factor for lumbar disc degeneration

Endplate pathology plays an important role in the development of lumbar disc degeneration. Previous research paid little attention to differences between the superior and inferior endplates as a possible risk factor for disc degeneration. The purpose of this study was to test the hypothesis that asymmetry between the superior and inferior endplates is a risk factor for the development of lumbar disc degeneration. A total of 134 patients with lumbar disc herniation (LDH) and 100 healthy adults (“Controls”) underwent magnetic resonance imaging scans. Each disc was categorized as non‐degenerated (Pfirrmann grades I–II) or degenerated (Pfirrmann grades III–V) and get the following three groups: “Degenerated LDH” discs (n = 145), “Non‐degenerated LDH” discs (n = 525) and “Non‐degenerated Control” discs (n = 500). On mid‐sagittal image, the lumbar endplate morphology could be categorized into three types: Flat, concave, and irregular. Superior and inferior endplates of a given disc were “symmetric” if both were of the same type, and “asymmetric” if they were of different types. The proportion of asymmetric endplates at L4–5 was higher in the “Degenerated LDH” discs group (47%) than in the “Non‐degenerated LDH” discs group (21%) or “Non‐degenerated Control” discs group (7%) (p < 0.05). At L5‐S1 the proportions were 73%, 55%, and 38% (p < 0.05). Asymmetry of superior and inferior endplates in the mid‐sagittal plane is a risk factor for lumbar disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2469–2475, 2018.

     

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。     

Drug‐induced changes to the vertebral endplate vasculature affect transport into the intervertebral disc in vivo

Intervertebral disc health is mediated in part by nutrient diffusion from the microvasculature in the adjacent subchondral bone. Evidence suggests that a reduction in nutrient diffusion contributes to disc degeneration, but the role of the microvasculature is unclear. The purpose of this study was to induce changes in the endplate microvasculature in vivo via pharmaceutical intervention and then correlate microvasculature characteristics to diffusion and disc health. New Zealand white rabbits were administered either nimodipine (to enhance microvessel density) or nicotine (to diminish microvessel density) daily for 8 weeks compared to controls. Trans‐endplate diffusion and disc health were quantified using post‐contrast enhanced magnetic resonance imaging (MRI). Histology was utilized to assess changes to the subchondral vasculature. Results indicate that nimodipine increased vessel area and vessel‐endplate contact length, causing a significant increase in disc diffusion. Surprisingly, nicotine caused increases in vessel number and area but did not alter diffusion into the disc. The drug treatments did affect the microvasculature and diffusion, but the relationship between the two is complex and dependent on multiple factors which include vessel‐endplate distance, and vessel‐endplate contact length in addition to vessel density. Our data suggest that drugs can modulate these factors to augment or diminish small molecule transport. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1694–1700, 2014.     

Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1‐34) in Ovariectomized Rats

Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1‐34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1‐34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1‐34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3‐month‐old female Sprague‐Dawley rats underwent L₄–L₅ posterolateral lumbar fusion (PLF) with spinous‐process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1‐34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion‐segment based on manual palpation. Greater new bone formation in histology was observed in PTH‐treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1‐34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1‐34) not only inhibited matrix degradation by decreasing MMP‐13, ADAMTS‐4 and Col‐I, but also promote matrix synthesis by increasing Col‐II and Aggrecan. In conclusion, PTH(1‐34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia. © 2015 American Society for Bone and Mineral Research.     

The influence of preoperative MRI findings on lumbar fusion clinical outcomes

Introduction

Spinal fusion as a treatment for degenerative disc disease is controversial. Prior authors have identified various MRI findings as being pain generators, which might help guide patient selection for lumbar fusion procedures. These findings have included disc desiccation, disc contour, high-intensity zone annular disruption, the presence of Modic endplate changes, and disc space collapse. The purpose of this study is to investigate which MRI findings in patients with degenerative disc disease predict clinical improvement with lumbar fusion.

Methods

A single-center surgical database of patients undergoing lumbar fusion was reviewed for patients whose indication for fusion surgery was primary disc pathology. We identified 51 patients (71 disc levels) who had completed 2-year prospectively collected outcomes questionnaires and had preoperative MRIs available for review. NRS (0–10) back and leg pain, Oswestry Disability Index (ODI) and SF-36 Physical Composite Summary scores were obtained preoperatively and at 1- and 2-year follow-up. MRIs were reviewed by three fellowship-trained spine surgeons who were asked to grade them for the following five characteristics: (a) disc desiccation, (b) disc contour, (c) presence of a high-intensity zone (HIZ) annular tear, (d) presence of Modic endplate changes and (e) disc height. Two-year outcome measures were compared to MRI findings to identify which findings correlated with improvement in outcome scores.

Results

Statistically significant improvements were noted in back pain, leg pain, SF-36 PCS and ODI in the group overall. Disc desiccation, disc contour, presence of an HIZ lesion, and the presence of Modic endplate changes did not correlate with 2-year outcomes. Disc height was correlated with 2-year change in outcome measures. Discs with preoperative height less than 5 mm demonstrated a 23.4 point ODI improvement compared to 9.2 points for discs >7 mm. Similarly, SF-36 PCS improved 9.5 points in discs <5 mm compared to 0.7 in discs greater than 7 mm. Discs between 5 and 7 mm demonstrated intermediate levels of improvement.

Conclusions

Several commonly utilized MRI criteria proposed as indications for lumbar fusion do not seem to correlate with 2-year improvement in clinical outcomes. Discs which are narrowed and collapsed, preoperatively, demonstrate better improvement at 2 years postoperatively as compared to discs which have maintained disc height. Significant disc space collapse may represent a subset of “degenerative disc disease” which responds more favorably to treatment with fusion.     

Sox9基因对兔腰椎间盘退变的作用

目的 观察腺病毒介导的Sox9基因(AdSox9)对兔腰椎间盘退变模型的疗效.方法 25只新西兰大白兔用针刺法制作腰椎间盘退变模型,24周后,将AdSox9注射到退变椎间盘组织中,6周后用MRI观察椎间盘变化,免疫组织化学法观察椎间盘组织Ⅱ型胶原(Col2al)的表达,逆转录-聚合酶链反应(RT-PCR)观察Col2al mRNA的变化.结果 MRI示:治疗后L2～3、L3～4、L4～5的椎间盘信号值分别为:580.43±76.43、612.74±56.73、605.87±76.53,模型对照组为:238.43±43.65、217.65±38.95、236.98±76.53;Col2al表达的标记指数:治疗后L2～3、L3～4、L4～5的椎间盘分别为:42.48±5.53、45.34±15.43、42.47±25.45,模型对照组为:11.68±10.08、12.68±13.75、13.38±26.53;Col2al mRNA的表达:治疗后L2～3、L3～4、L4～5的椎间盘分别为6570.43±174.53、7653.75±158.93、6905.83±119.23,模型对照组为:1256.76±89.76、1217.65±18.65、1132.97±47.65.3种方法均示,治疗组与模型对照组之间比较差异有统计学意义(P<0.01).结论 AdSox9对退变椎间盘动物模型有治疗作用.     

A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype

The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types—notochordal cells (NCs) and non‐notochordal chondrocyte‐like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI‐positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin‐8‐ and galectin‐3‐co‐positive cells, identified as NCs. The proportion of TUNEL‐positive cells, which predominantly comprised non‐NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up‐regulation of ADAMTS‐5 in the 1‐day loaded group and MMP‐3 in the 7‐day loaded group. Aggrecan‐1 and collagen type 2α‐1 mRNA levels were down‐regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:455–463, 2014.     

终板下椎体缺血诱导兔椎间盘退行性变模型的建立及终板中内皮素1的表达

目的通过终板下注射无水乙醇阻碍椎体-终板营养,建立一种新型兔腰椎椎间盘退行性变模型,并观察终板退行性变过程中内皮素1(ET-1)的表达情况。方法健康4月龄新西兰兔32只,随机分成4组,每组8只,选取L5,6椎体(对应L4/L5及L5/L6椎间盘)注射300μL无水乙醇,选取L4椎体(对应L3/L4椎间盘)注射磷酸盐缓冲液(PBS)作为实验对照,L7椎体(对应L6/L7椎间盘)未注入任何物质作为正常对照。其中1组造模后1个月提取软骨终板细胞,行免疫细胞化学染色检测ET-1表达;余3组分别于造模后1、3和5个月进行椎间盘X线和MRI检查,取椎间盘组织行HE染色观察形态学改变,免疫组织化学染色观察ET-1表达。结果注射无水乙醇后,随着时间进展,X线片显示椎间隙高度显著下降、椎间隙变窄、边缘骨赘增生,MRI T2WI显示椎间盘低信号;苏木精-伊红染色(HE)显示终板的生长板厚度变薄,终板结构破损,同时软骨终板细胞退化、直至消失,髓核中细胞发生转化(由空泡细胞转变为软骨样细胞,进而形成纤维软骨样细胞)造成髓核纤维化,纤维环结构排列紊乱、纤维化程度逐步加重;免疫组织化学染色显示,发生退行性变的终板组织内有ET-1表达,但随着退行性变加剧,ET-1表达强度下降;提取的退行性变软骨终板细胞(造模后1个月)也显示细胞质内ET-1强表达。结论通过注射无水乙醇阻碍椎体-终板营养途径可成功建立兔椎间盘退行性变模型,终板退行性变过程中伴随ET-1的表达。     

不同程度退变的软骨终板的影像学变化及其临床意义

目的：从影像学角度研究腰椎间盘不同程度退变时终板在矢状面和横断面的形态变化规律，探讨其临床意义。方法：本研究选取58例L4．5椎间盘呈退行性改变的影像学资料（MRI、CT）进行研究（其中椎间盘突出者34例），分别将其矢状位MRI T2WI成像采用MRI机内Mean／Curve测量软件测量L4．5运动节段退变的椎间盘与相应节段脑脊液平均信号强度比值，判断椎间盘退变程度进行分组。分为3组：轻度退变组17例，中度退变组17例，重度退变组24例。同时采用正中矢状位MRI T2WI成像分别测量相应椎间（L4．5）终板于矢状面上的凹陷角。另外借助L4．5椎间CT平扫成像测量其相邻终板的最大前后径和横径，计算终板的相对曲率，分析椎间盘在不同退变程度下椎体终板凹陷角及其相对曲率的变化规律，并探讨椎体终板的凹陷角与其相对曲率的相关性。结果：①椎体终板（L4下终板，L5上终板）凹陷角均随着相应椎间盘退变程度加重而增大，重度退变组与中度、轻度退变组（L4下终板、L5上终板）凹陷角差异均有统计学意义（P〈0．01）。②重度退变组与轻度退变组（L4下终板、L5上终板）相对曲率差异有统计学意义（P〈0．01），中度退变组与轻度退变组（L4下终板、L5上终板）相对曲率差异有统计学意义（P〈0．01），中度退变组与重度退变组（L4下终板、k上终板）相对曲率差异无统计学意义（P〉0．05）。⑧终板凹陷角与其相对曲率呈正相关关系（r：0．786，0．490）。结论：椎体终板的凹陷角与相对曲率随着椎间盘退变程度加重而发生相应变化，这种变化是腰椎间盘退变突出、椎间盘源性下腰痛的重要因素，且椎体终板的凹陷角与其相对曲率存在着相关关系，故可以通过凹陷角的变化判断其相对曲率的改变，评估椎间盘突出的概率。     

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。     

Structural,compositional, and biomechanical alterations of the lumbar spine in rats with mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome)

Mucopolysaccharidosis (MPS) VI is an inherited lysosomal storage disorder resulting from deficiency of N‐acetylgalactosamine‐4‐sulfatase activity and subsequent accumulation of incompletely degraded dermatan sulfate (DS) containing glycosaminoglycans (GAGs). Painful spinal deformities are commonly found in MPS VI patients. We characterized lumbar spine structure, composition, and biomechanics in a naturally occurring rat MPS VI model and evaluated the role of MMP‐13, ADAMTS‐5 and TNF‐α in modulating the observed changes. MPS VI rats had discs with large vacuolated cells and sizable nuclear defects. MPS spine segments also had structural and functional changes suggestive of spinal instability, including decreased nuclear pressurization, increased joint laxity and increased disc height index. These functional changes were at least partly associated with elevated ADAMTS‐5, MMP‐13, and TNF‐α. Vertebral and endplate biomechanics were also affected by MPS VI with decreased failure load and stiffness. The discal and vertebral dysfunctions observed in MPS VI rats are likely to be associated with pathological spinal conditions, similar to those that afflict MPS patients. Our findings also suggest more broadly that abnormal accumulation of GAGs and the associated chronic pro‐inflammatory and catabolic cascade may also be a source of spinal dysfunction. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 621–631, 2013     

Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model

Purpose

Previous studies have shown that blocking the endplate nutritional pathway with bone cement did not result in obvious intervertebral disc degeneration (IDD) in mature animal models. However, there are very few comparable studies in immature animal models. As vertebroplasty currently is beginning to be applied in young, even biologically immature patients, it is important to investigate the effect of cement blocking at the endplate in an immature animal model.

Methods

Two lumbar intervertebral discs in eight immature pigs were either blocked by cement in both endplate pathways or stabbed with a scalpel in the annulus fibrosus (AF) as a positive control, and with a third disc remaining intact as a normal control. Magnetic resonance imaging (MRI) and histology study were performed.

Results

After three months, the cement-blocked discs exhibited severe IDD, with the percentage of disc-height index (DHI), nucleus pulposus (NP) area, and NP T2 value significantly lower than the normal control. These IDD changes were histologically confirmed. Post-contrast MRI showed diseased nutritional diffusion patterns in the cement-blocked discs. Moreover, the degenerative changes of the cement-blocked discs exceeded those of the injured AF positive controls.

Conclusions

The endplate nutritional pathway was interfered with and diseased after three months of bone cement intervention in an immature porcine model. Severe interference in the endplate nutritional pathway in an immature porcine model caused IDD. These findings also draw attention to the fact that interference in endplate nutritional pathways in immature or young patients may affect the vitality of adjacent discs.     

Association between ADAMTS‐4 gene polymorphism and lumbar disc degeneration in Chinese Han population

Low back pain (LBP) is a common health problem and many LBP are caused by lumbar disc degeneration (LDD). ADAMTS‐4 (a disintegrin and metalloprotease with thrombospondin motifs‐4), also known as aggrecanse‐1, plays a core role in degeneration of extracellular matrix in LDD. To investigate the association between ADAMTS‐4 genetic polymorphism and LDD, we genotyped SNPs in and around ADAMTS‐4. We recruited 482 sporadic cases of LDD and 496 healthy controls from Chinese Han population. Five SNPs were selected and phenotyped by the Sequenom MassARRAY system. Allelic, genotypic, and haplotypic association was performed. Rs4233367 (c.1877 C>T), which located in exon of ADAMTS‐4 showed significant association with LDD. The T allele conferred a lower risk of LDD with an OR of 0.69 and TT genotype is at nearly one‐fifth of the risk compared to CC genotype. Other tested SNPs didn't show significant difference between the case and control groups. The SNP rs4233367 in the exon of ADAMTS‐4 gene may be associated with lumbar disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:860–864, 2016.