Stable mechanical environments created by a low-tension traction device is beneficial for the regeneration and repair of degenerated intervertebral discs

BACKGROUNDBy blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful.PURPOSEIn the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration.STUDY DESIGNA macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction.METHODSSix-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7−Co10], while Co8−Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8−Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate.RESULTSAfter 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8–Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D–G). In addition, histologic scores of the intervention groups (D–G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D–G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF.CONCLUSIONSDegenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction.     

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.     

Nucleus pulposus degeneration alters properties of resident progenitor cells

Background contextThe intervertebral disc (IVD) possesses a minimal capability for self-repair and regeneration. Changes in the differentiation of resident progenitor cells can represent diminished tissue regeneration and a loss of homeostasis. We previously showed that progenitor cells reside in the nucleus pulposus (NP). The effect of the degenerative process on these cells remains unclear.PurposeWe sought to explore the effect of IVD degeneration on the abundance of resident progenitor cells in the NP, their differentiation potential, and their ability to give rise to NP-like cells. We hypothesize that disc degeneration affects those properties.Study designNucleus pulposus cells derived from healthy and degenerated discs were methodically compared for proliferation, differentiation potential, and ability to generate NP-like cells.MethodsIntervertebral disc degeneration was induced in 10 skeletally, mature mini pigs using annular injury approach. Degeneration was induced in three target discs, whereas intact adjacent discs served as controls. The disc degeneration was monitored using magnetic resonance imaging for 6 to 8 weeks. After there was a clear evidence of degeneration, we isolated and compared cells from degenerated discs (D-NP cells [NP-derived cells from porcine degenerated discs]) with cells isolated from healthy discs (H-NP cells) obtained from the same animal.ResultsThe comparison showed that D-NP cells had a significantly higher colony-forming unit rate and a higher proliferation rate in vitro. Our data also indicate that although both cell types are able to differentiate into mesenchymal lineages, H-NP cells exhibit significantly greater differentiation toward the chondrogenic lineage and NP-like cells than D-NP cells, displaying greater production of glycosaminoglycans and higher gene expression of aggrecan and collagen IIa.ConclusionsBased on these findings, we conclude that IVD degeneration has a meaningful effect on the cells in the NP. D-NP cells clearly go through the regenerative process; however, this process is not powerful enough to facilitate full regeneration of the disc and reverse the degenerative course. These findings facilitate deeper understanding of the IVD degeneration process and trigger further studies that will contribute to development of novel therapies for IVD degeneration.     

Association and histological characteristics of endplate injury and intervertebral disc degeneration in a rat model

IntroductionThe purpose of this study was to construct a rat caudal vertebral body fracture model and to analyze the association and histological characteristics of vertebral body fracture with endplate injury and adjacent intervertebral disc degeneration.Materials and methodsThis study included 144 clean-grade male Sprague-Dawley rats, which were randomly divided into a control, middle vertebral body injury (MI), and endplate injury (EI) groups. A vertebral body fracture with or without endplate injury was developed by either drilling a hole in the middle of a rat caudal vertebral body to create a fracture with an intact endplate or drilling a hole in the vertebral body near the intervertebral disc to create a vertebral body fracture with endplate injury. The histological differences in the adjacent intervertebral discs of vertebral body fractures with or without endplate injury were detected using imaging, non-specific histological staining, immunohistochemistry and TUNEL assay.ResultsImaging results revealed that the EI group showed a significant decrease in intervertebral space height and intervertebral disc T2 signal over time. Non-specific histological staining revealed that in the EI group, the intervertebral disc was degenerative. Immunohistochemistry indicated that Aggrecan and Collagen-II were decreased and inflammatory factors were increased in the EI group. The TUNEL detection found that apoptosis was significantly increased in the EI group as compared with the MI and control groups.ConclusionIn rat caudal vertebral body fractures, a fracture with endplate injury is more likely to induce or accelerate degeneration of adjacent intervertebral discs.     

Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients

Background contextExisting research on lumbar disc degeneration has remained inconclusive regarding its etiology, pathogenesis, symptomatology, prevention, and management. Degenerative disc disease (DDD) and disc prolapse (DP) are common diseases affecting the lumbar discs. Although they manifest clinically differently, existing studies on disc degeneration have included patients with both these features, leading to wide variations in observations. The possible relationship or disaffect between DDD and DP is not fully evaluated.PurposeTo analyze the patterns of lumbar disc degeneration in patients with chronic back pain and DDD and those with acute DP.Study designProspective, magnetic resonance imaging–based radiological study.MethodsTwo groups of patients (aged 20–50 years) were prospectively studied. Group 1 included patients requiring a single level microdiscectomy for acute DP. Group 2 included patients with chronic low back pain and DDD. Discs were assessed by magnetic resonance imaging through Pfirmann grading, Schmorl nodes, Modic changes, and the total end-plate damage score for all the five lumbar discs.ResultsGroup 1 (DP) had 91 patients and group 2 (DDD) had 133 patients. DP and DDD patients differed significantly in the number, extent, and severity of degeneration. DDD patients had a significantly higher number of degenerated discs than DP patients (p<.000). The incidence of multilevel and pan-lumbar degeneration was also significantly higher in DDD group. The pattern of degeneration also differed in both the groups. DDD patients had predominant upper lumbar involvement, whereas DP patients had mainly lower lumbar degeneration. Modic changes were more common in DP patients, especially at the prolapsed level. Modic changes were present in 37% of prolapsed levels compared with 9.9% of normal discs (p<.00). The total end-plate damage score had a positive correlation with disc degeneration in both the groups. Further the mean total end-plate damage score at prolapsed level was also significantly higher.ConclusionThe results suggest that patients with disc prolapse, and those with back pain with DDD are clinically and radiologically different groups of patients with varying patterns, severity, and extent of disc degeneration. This is the first study in literature to compare and identify significant differences in these two commonly encountered patient groups. In patients with single-level DP, the majority of the other discs are nondegenerate, the lower lumbar spine is predominantly involved and the end-plate damage is higher. Patients with back pain and DDD have larger number of degenerate discs, early multilevel degeneration, and predominant upper lumbar degeneration. The knowledge that these two groups of patients are different clinically and radiologically is critical for our improved understanding of the disease and for future studies on disc degeneration and disc prolapse.     

A small-molecule inhibitor of the Wnt pathway,lorecivivint (SM04690), as a potential disease-modifying agent for the treatment of degenerative disc disease

BACKGROUND CONTEXTAbnormal Wnt signaling in intervertebral discs (IVDs) progresses degenerative disc disease (DDD) pathogenesis by impairing nucleus pulposus cell function, decreasing matrix deposition, and accelerating fibrosis.PURPOSEThis study was conducted to evaluate the effects of lorecivivint (LOR; SM04690), a small-molecule Wnt pathway inhibitor, on IVD cells and in an animal model of DDD.STUDY DESIGNWe used in vitro assays and a rat model of DDD to test the effects of LOR on nucleus pulposus cell senescence and viability, annulus fibrosus (AF) cell fibrosis, and cartilage regeneration and protection.METHODSWnt pathway gene expression was measured in human NP and AF cell cultures treated with LOR or DMSO (vehicle). Chondrocyte-like differentiation of rat and human NP cells, NP cell senescence and protection, and AF cell fibrosis were assessed using gene expression and immunocytochemistry. Disc and plasma pharmacokinetics were analyzed following intradiscal LOR injection in rats. In vivo effects of LOR and vehicle on AF integrity, AF/NP junction, NP cellularity and matrix, and disc height were compared using histopathology and radiography in a rat coccygeal IVD needle-puncture model of DDD.RESULTSIn NP and AF cell cultures, LOR-inhibited Wnt pathway gene expression compared with vehicle. In NP cells, LOR inhibited senescence, decreased catabolism, and induced differentiation into chondrocyte-like cells; in AF cells, LOR decreased catabolism and inhibited fibrosis. A single intradiscal LOR injection in rats resulted in therapeutic disc concentrations (~30 nM) for >180 days and minimal systemic exposure. DDD-model rats receiving LOR qualitatively demonstrated increased cartilage matrix and reduced AF lamellar disorganization and fragmentation with significantly (p<.05) improved histology scores and increased disc height compared with vehicle.CONCLUSIONSLOR showed beneficial effects on IVD cells in vitro and reduced disease progression in a rat model of DDD compared with vehicle, suggesting that LOR may have disease-modifying therapeutic potential.CLINICAL SIGNIFICANCEThe current therapeutic options for DDD are pain management and surgical intervention; there are no approved therapies that alter the progression of DDD. Our data support advancing LOR into clinical development as an injectable, small-molecule, potential disease-modifying treatment for DDD in humans.     

Inflammaging determines health and disease in lumbar discs—evidence from differing proteomic signatures of healthy,aging, and degenerating discs

BACKGROUND CONTEXTThe true understanding of aging and disc degeneration (DD) is still elusive. MRI has not helped our attempts to understand the health and disease status of the discs as it reflects mainly the end morphologic changes and not the changes at a molecular level. Understanding degeneration at a molecular level through proteomics might allow differentiation from normal aging and also aid in the development of biomarkers for early diagnosis and preventive therapies.PURPOSETo utilize proteomics to understand the molecular basis of healthy, aging, and degenerating discs and conclusively differentiate normal aging and degeneration.STUDY DESIGNProteomic analysis of human intervertebral disc samples.METHODSL4–L5 disc samples from three groups were acquired and subjected to proteomic analysis. Samples from individuals aged in the second, third, and fourth decades were used to represent young healthy discs (Group A). Those from MRI normal donors aged in the fifth, sixth, and seventh decades represented normal aging (Group B). Five degenerated discs obtained from patients at surgery represented degeneration (Group C). The entire proteome map and alteration in protein expressions were further analyzed using bioinformatics analysis. This was a self-funded project.RESULTSThere were 84 common proteins. Specific proteins numbered 225 in A, 315 in B, and 283 in C. By gene ontology biological process identification, Group A predominated with extracellular matrix organization, cytoskeletal structural and normal metabolic proteins. Group B differed in having additional basal expression of immune response, complement inhibitors, and senescence proteins. Group C was different, with upregulation of proteins associated with oxidative stress response, positive regulators of apoptosis, innate immune response, complement activation and defense response to gram positive bacteria indicating ongoing inflammaging.CONCLUSIONSOur study documented diverse proteome signatures between the young, aging and degenerating discs. Inflammaging was the main differentiator between normal biological aging and DD.CLINICAL SIGNIFICANCEMultiple inflammatory molecules unique to DD were identified, allowing the possibility of developing specific biomarkers for early diagnosis and thereby provide evidence-based metrics for preventive measures rather than surgical intervention and also to monitor progress of the disease.     

A novel rabbit disc degeneration model induced by fibronectin fragment

ObjectiveTo establish a novel and useful rabbit model of lumbar disc degeneration using microinjection of a fibronectin fragment.MethodsThirty-two rabbits underwent injection of N-terminal 30 kDa fibronectin fragment (Fn-f) (Group A, n = 12; Group B, n = 4) or phosphate buffered saline (PBS) (Group C, n = 12; Group D, n = 4) into the lumbar discs using a 32-gauge microsyringe. Two rabbits (Group E) with no treatment were sacrificed to examine the proteoglycan synthesis of neucleus pulposus (NP) using ³⁵S-sulfate incorporation assay. At the 4-, 8-, 12-, and 16-week time points, the discs were examined histologically, radiographically and with proteoglycan synthesis.Results(1) Histology demonstrated a progressive loss of cell numbers in NP and architecture disorganization in NP and annulus fibrosus (AF) over the study period. (2) Radiology: comparing with the PBS-injected discs, the Fn-f-injected discs exhibited no significant differences in disc heights at the 4-week time point, but significant decreases in disc heights at the 8-, 12-, and 16-week time points (P < 0.01). Apparent anterior osteophytes formed at the 12-week time point and enlarged remarkably by the 16-week time point in the Fn-f-injected spines. (3) Protoglycan synthesis in the Fn-f-injected discs decreased progressively (P < 0.01). At each time point, the Fn-f-injected discs showed significantly decreased proteoglycan synthesis compared with controls (P < 0.05 or P < 0.01).ConclusionsFn-f induced a progressively degenerative process in rabbit discs, which was consistent with the spontaneous degeneration in human. Fn-f induced degeneration seemed to be a novel and useful model for the study of disc degeneration at the molecular level.     

Effect of endplate reduction on endplate healing morphology and intervertebral disc degeneration in patients with thoracolumbar vertebral fracture

Objective

To determine the effect of endplate reduction on the final healing morphology and degenerative changes in intervertebral discs.

Methods

Forty-eight patients with single-level thoracolumbar fractures with endplate injury were included. All patients underwent posterior reduction and pedicle screw fixation, and postoperative imaging was used to determine whether endplate reduction was successful. The healing morphology of the endplate was divided into three types: increased endplate curvature, irregular healing and traumatic Schmorl node. MRI was performed at baseline and at the last follow-up evaluation to observe changes in disc degeneration (disc height and nucleus pulposus signal) and Modic changes.

Results

The reduction rate in the central area was significantly lower than that in the peripheral area (P = 0.017). In patients with successful reduction, 90.9% (20/22) of the endplates healed with increased curvature. In patients with an unsuccessful endplate reduction, 63.4% (26/41) of the endplates healed irregularly, and 34.1% (14/41) of the endplates formed traumatic Schmorl nodes. Endplate reduction was closely related to the final healing morphology of the endplate (P < 0.001), which had a significant protective effect on the degeneration of the intervertebral disc. At the last follow-up evaluation, there was no statistically significant correlation between different endplate healing morphologies and new Modic changes.

Conclusions

The reduction rate in the central area is significantly lower than that in the peripheral area. Although all of the intervertebral discs corresponding to fractured endplates had degenerated to different degrees, successful endplate fracture reduction can obviously delay the degeneration of intervertebral discs.

     

Anterior cervical plating technique to prevent adjacent-level ossification development

Background contextThe proximity (<5 mm) of the plate to the adjacent disc space is known to be a critical risk factor for adjacent-level ossification development (ALOD). As plates provide many advantages including higher fusion rates and improved alignment, their use will continue. Instead, it is necessary to modify the plating techniques to minimize this complication.PurposeTo determine if our newer plating technique decreases the incidence of ALOD after anterior cervical plating.Study designRetrospective matched cohort analysis of preoperative and postoperative radiographic data.Patient sampleOne hundred patients were classified into two groups; conventional (C) and new (N) plating techniques. The control group (Group C) was matched to the study group (Group N) in a 1:1 fashion using matching criteria of age (within 5 years), gender, number of fusion levels, and comorbidities, including diabetes and tobacco use.Outcome measuresThe lateral plain X-rays of cervical spine taken at postoperative 6 months and 2 years were used for analysis.MethodsIn Group N, the cranial and caudal screws were started at the anterior end plate corners and angled away from the end plates so as to use the shortest possible plate and maximize the distance to the adjacent end plates. Group C was the historical control using a longer plate with more orthogonal screw angulation. On postoperative 6-week lateral films, the distances from the tip of the plate to both cranial and caudal adjacent discs (plate-to-disc distances) were measured. Based on the postoperative 2-year radiographs, the incidence of ALOD was determined, and the severity of ossification was classified on a scale ranging from Grade 0 (no ossification) to Grade 3 (complete bridging).ResultsMean plate-to-disc distances in Group N were significantly longer at both cranial and caudal adjacent levels than those in Group C (p<.001). The incidence of ALOD was significantly lower in Group N than in Group C, both at the cranial adjacent disc spaces (42% vs. 72%) and caudal adjacent disc spaces (20% vs. 42%) (p<.05). Severe ossification (Grade 2 or greater) also developed less frequently in Group N at cranial and caudal levels (6% vs. 20%, respectively; p<.05).ConclusionsThe new technique of using a shorter plate with longer angulated screws resulted in significantly reduced incidence and severity of ALOD.     

Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study

The immature disc nucleus pulposus (NP) consists of notochordal cells (NCs). With maturation NCs disappear in humans, to be replaced by chondrocyte-like mature NP cells (MNPCs); this change in cell phenotype coincidences with early signs of disc degeneration. The reasons for NC disappearance are important to understand disc degeneration, but remain unknown, yet. This study investigated, whether loading induced a change from a notochordal nucleus phenotype to a chondrocyte-like one. An in vivo disc compression model with fixateur externe was used in 36 mature rabbits. Discs were compressed for different time periods (1, 28, 56 days), and compared with uncompressed control discs (56 days without treatment), and discs with sham compression (28 days). Nucleus cell phenotype was determined by histology and immunohistochemistry. NCs, but not MNPCs highly expressed bone-morphogenetic-protein 2 and cytokeratin 8, thus NC and MNPC numbers could be determined. A histologic score was used to detect structural endplate changes after compression (28 days). Control and sham compressed discs contained around 70% NCs and 30% MNPCs, to be decreased to <10% NCs after 28–56 days of loading. NC density fell sharply by >50% after 28–56 days of compression (P < 0.05 vs. controls). Signs of decreased endplate cellularity and increased endplate sclerosis and fibrosis were found after loading. These experiments show that NCs were less resistant to mechanical stress than MNPCs suggesting that increased intradiscal pressures after loading, and limited nutrition through structurally altered endplates could instigate the disappearance of NCs.     

Disc degeneration reduces the delamination strength of the annulus fibrosus in the rabbit annular disc puncture model

Background contextDegenerative disc disease is a common pathologic disorder accompanied by both structural and biochemical changes. Changes in stress distribution across the disc can lead to annulus fibrosus (AF) damage that can affect the strength and integrity of the disc. Given that some present degeneration therapies incorporate biological regrowth of the nucleus pulposus (NP), it is crucial that the AF remains capable of containing this newly grown material.PurposeTo examine the resistance of AF to delamination using an adhesive peel test in experimentally degenerated rabbit discs.Study designExperimentally induced disc degeneration; excised AF tissue study.MethodsDisc degeneration was induced in eight New Zealand white rabbits by annular puncture; four additional rabbits served as controls. In experimental rabbits, an 18-gauge needle was inserted into the anterolateral AF region of levels L2–L3 and L4–L5, and disc height was monitored by X-ray. Animals were sacrificed at 4 and 12 weeks postsurgery and magnetic resonance images and X-rays were taken. Four discs were excised from the experimental animals; two punctured (L2–L3 and L4–L5) and two controls (L3–L4 and L6–L7). The same four discs were also excised from the age-matched control animals and served as nonpunctured control discs. To determine resistance to delamination, AF samples were dissected from each disc and subjected to a mechanical peel test at 0.5 mm/s.ResultsMagnetic resonance imaging and X-ray images confirmed dehydration of the NP and reduced disc height, similar to that found in clinical degeneration. Resistance to delamination was significantly lower in punctured/degenerated discs compared with both the nonpunctured discs from the same animal (27% lower) and the nonpunctured control discs (30% lower) (p=.024).ConclusionsThe findings of this study suggest that degeneration increases the potential for delamination between AF layers. Given this substantial change to the integrity of the AF after degeneration, clinical treatments should not only target rehydration or regrowth of the NP, but should also target repair and strengthening of the AF to confine the NP.     

Morphologic comparison of cervical, thoracic, lumbar intervertebral discs of cynomolgus monkey (Macaca fascicularis)

The aim was to analyze the morphological differences of the intervertebral disc and endplates at different levels. Forty-five vertebral motion segments were obtained from the spine of nine 3 to 4-year-old cynomolgus monkeys (Macaca fascicularis). From every spine, five discs were sectioned (C5–C6, T3–T4, T9–T10, L2–L3, L4–L5). In all the groups, tissue samples were collected and sections were stained with Masson’s trichrome, Safranine-O and van Gieson’s connective tissue stain to analyze the intervertebral discs. Immunohistochemistry was performed, using specific antibodies to detect collagens I and II. The intervertebral disc height, the maximum nucleus pulposus height, the superior and inferior endplate heights were histomorphometrically measured and different indexes were calculated to compare the differences between specimens of the same animal and between discs of the same level, and finally the differences between groups of discs of different levels. There were no differences existing in annular fibers anchoring on the endplate between discs of different levels. A positive immune reaction for type I collagen was observed in the longitudinal ligaments and in the annular region adjacent to them. Collagen II immune reactivity was found in the annulus close to the nucleus pulposus, in the endplates and in the nucleus. There were no differences between discs of different levels in the collagen I and II localization. The height of the discs varied along the spine. The smallest value was measured in T3–T4, with a larger increase caudally than cranially. The highest value was measured in L2–L3. A cervical disc was 55% the height of a lumbar one. The endplate height increased along the length of the spine. The inferior EP was always higher than the superior. The study provides a detailed structural characterization of the intervertebral disc and may be useful for further investigations on the disc degeneration process. An erratum to this article can be found at     

兔退变椎间盘体内转染hTGF-β1、β3的生物学效应

目的 应用重组腺相关病毒2(recombinant adeno-associated virus,rAAV2)介导人转化生长因子β1(human transforming growth factor-β1,hTGF-β1)和β3(hTGF-β3)单基因或双基因联合体内转染退变兔髓核细胞,观察基因产物的表达及其对基质成分...     

椎体终板损伤对兔椎问盘髓核Ⅰ、Ⅱ型胶原的影响

目的 观察椎体终板损伤对兔椎间盘髓核Ⅰ、Ⅱ型胶原的影响并探讨其机制.方法 4个月龄清洁级日本大白兔12只,完整取出40个包含终板的完整椎间盘(L2-L5),随机分为实验组和对照组,每组20个.实验组参考Daniel Haschtmann的方法建立终板损伤模型.椎间盘整体培养2周后,免疫组织化学方法观察椎间盘髓核中Ⅰ、Ⅱ型胶原的表达情况,并用HMIAS-2000图像分析系统进行半定量分析.结果 免疫组织化学染色显示:实验组椎间盘髓核Ⅰ型胶原的表达比对照组高;而Ⅱ型胶原的表达则比对照组低,差异均有统计学意义(P<0.05).结论 外伤致椎体终板损伤后会导致椎间盘髓核Ⅰ、Ⅱ型胶原的变化,继而加速椎间盘退行性变.     

颈椎终板Modic改变在颈肩痛病例中的分布和相关因素分析

目的 探讨颈椎终板Modic改变在颈肩痛病例中的临床分布特点,并探讨其发生的相关因素.方法 选择2006年一年内因颈肩痛而在本院行颈椎MR和常规X线检查的患者共1023例,回顾性分析颈椎MR中所表现的Modic改变在人群、椎间盘节段、年龄、颈椎曲度和椎间盘退变分级中的分布特点以及其发生的相关因素.结果 1023例共计6138个颈椎椎间盘中90例(8.8％),108(1.8％)个椎间盘邻近终板发生Modic改变.I型32例(3.1％),34个椎间盘(0.6％);Ⅱ型55例(5.4％),71个椎问盘(1.2％)Ⅲ型3例(0.3％),3个椎间盘(0.06％).按照各个椎间盘节段发病数统计,C2-3 O个、C3-4 10个、C415 18个、C5-6 52个、C6-7 23个、C7 T1 5个,发病率分别为O％、0.2％、0.4％、1.0％、0.4％、0.1％.Modic改变和椎间盘退变明显相关(P=0.000).40岁以上是Modic改变发生较多的年龄段(P=0.000).通过Binary Logistic检验逐步回归法得出回归方程为y=一15.514+3.047D+0.684C+0.210L+0.152,4(y为Modic改变、A为年龄、L为椎问盘节段、D为椎间盘退变程度、C为Cobb角分组),P=0.000,EXP值,D=21.048,C=I.982,L=1.233,A=1.164.结论 颈椎终板Modic改变发生率较腰椎低,其发生和椎间盘退变、椎间盘节段、年龄和颈椎曲度之间存在相关性,椎问盘退变是最重要的影响因素.Ⅱ型最为多见,I型次之,Ⅲ型最为少见,多发生于C3-6椎间盘.40岁以上是Modie改变易发年龄.     

MRI and histology of collagen template disc implantation and regeneration in rabbit temporomandibular joint: preliminary report

INTRODUCTION: We aimed to evaluate regeneration of injured temporomandibular joint (TMJ) discs following reconstituted collagen template implantation in rabbits using contrast-enhanced magnetic resonance imaging (MRI) and to correlate these findings with histology. METHODS: Twenty-four adult rabbits were divided into five groups: group A, partial discectomy without implantation (n = 6); group B, partial discectomy with collagen template implantation (n = 6); group C, partial discectomy with subdermal graft implantation (n = 6); group D, sham operation (n = 4); and group E, control (n = 2). All rabbits received baseline MRI scans before surgery and follow-up MRI studies at 3 months after surgery. All rabbits were sacrificed for histologic analysis after the follow-up MRI. RESULTS: In group A, follow-up MRI showed marked joint effusion in all six injured TMJs, which was accompanied by bony erosion at the tympanic fossa and mandibular condyle. In group B, MRI showed a homogenous low signal intensity in five of six discs, suggestive of regeneration. One disc showed higher signal intensity at its lateral portion than that of the original disc, indicating partial regeneration. MRI of group C depicted a low signal intensity, bandlike regenerative structure in four of the six discs. One disc with partial regeneration demonstrated relatively high signal intensity. The disc in the sixth animal of this group showed no evidence of regeneration. All of the MRI findings were in agreement with the histologic findings. CONCLUSION: TMJ discs can regenerate following implantation of a reconstituted collagen template in discectomied rabbits. Contrast-enhanced MRI can be used to monitor and determine the degree of disc regeneration.     

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.