The effects of dynamic loading on the intervertebral disc

Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of ‘physiological’ loading may also be an important factor for the differentiation of stem cells towards most ideally ‘discogenic’ cells for tissue engineering purpose.     

Intradiscal pressure depends on recent loading and correlates with disc height and compressive stiffness

Purpose

Intervertebral discs exhibit time-dependent deformation (creep), which could influence the relation between applied stress and intradiscal pressure. This study investigates the effect of prolonged dynamic loading on intradiscal pressure, disc height and compressive stiffness, and examines their mutual relationships.

Methods

Fifteen caprine lumbar discs with 5 mm of vertebral bone on either side were compressed by 1 Hz sinusoidal load for 4.5 h. After preload, ‘High’ (130 ± 20 N) or ‘Low’ (50 ± 10 N) loads were alternated every half hour. Continuous intradiscal pressure measurement was performed with a pressure transducer needle.

Results

Each disc showed a linear relationship between axial compression and intradiscal pressure (R ² > 0.91). The intercept of linear regression analysis declined over time, but the gradient remained constant. Disc height changes were correlated to intradiscal pressure changes (R ² > 0.98): both decreased during High loading, and increased during Low loading. In contrast, compressive stiffness increased during High loading, and was inversely related to intradiscal pressure and disc height.

Conclusions

Intradiscal pressure is influenced by recent loading due to fluid flow. The correlations found in this study suggest that intradiscal pressure is important for disc height and axial compliance. These findings are relevant for mechanobiology studies, nucleus replacements, finite element models, and ex vivo organ culture systems.     

Effects of running on intervertebral disc height

Vertebral column height decreases throughout the course of the day. This decrease is the result of a loss of fluid from the intervertebral discs due to compressive loading. When the load changes during the day, as a result of varying physical activities, the rate of disc shrinkage changes in relation to those activities. The purpose of this study was to determine if there is a correlation between long distance running and an increase in the loss of vertebral column height. Thirty elite male runners, ages 17 to 29, participated in this study. Subjects' vertebral column heights were measured in the morning upon waking, in the afternoon prior to running 9 miles, and then immediately following the run. Paired t-tests revealed: 1) that the vertebral column height was significantly less following the run, and 2) that a significantly greater amount of height was lost during 1 hour of running than during 7.5 hours of relatively static activities. J Orthop Sports Phys Ther 1990;12(4):139-146.     

经皮激光腰椎间盘减压术后腰椎关节突关节和椎间高度的变化

目的：观察经皮激光椎间盘减压术（percutaneous laser disc decompression，PLDD）治疗腰椎间盘突出症术后腰椎关节突关节和椎间高度的变化。方法：应用半导体激光系统对32例腰椎间盘突出症患者进行PLDD治疗。29例患者为单节段突出，其中L3/4 3例，L4／5 18例，L5/S1 8例；3例患者同时合并IA／5和L5/S1节段突出。利用Macnab标准评价随访患者的疗效，并观察术前、术后椎间盘突出节段关节突关节角的形态，测量L3，4、L4/5和L5／S1椎间高度指数和椎间盘突出节段关节突关节角的角度。结果：所有患者无术中和术后并发症。随访14～22个月，平均17个月，按Macnab标准评价：优14例（43．75％），良13例（40．63％）；可3例（9．37％），差2例（6．25％），优良率84．38％。术后L5/S1椎间高度指数与术前相比显著性下降（P〈0．05），但L3/4和L4／5椎间高度指数无显著性改变；关节突关节无明显退变；L4／5和L5／S1椎间盘突出侧的关节突关节角角度显著性下降（P〈0．05），但L3/4椎间盘突出侧的关节突关节角度无显著性改变。结论：经皮激光腰椎间盘减压术后患者的L5／S1椎间高度和腰椎间盘突出侧关节突关节角角度下降．有可能增加腰椎滑脱的风险。     

Anti-apoptotic effects of caspase inhibitors on rat intervertebral disc cells

BACKGROUND: Apoptosis is thought to be a critical component of disc degeneration. Two main pathways of Fas-mediated apoptosis have been identified: Type I, which is the death-inducing signaling complex pathway, and Type II, which is the mitochondrial pathway. The apoptotic pathway for anulus fibrosus cells, which is phenotypically different from that of nucleus pulposus cells, has not been elucidated to our knowledge. The ultimate initiators or executioners of apoptosis are caspases. There are also inhibitors of caspases, which have the potential of being used as anti-apoptotic therapeutic agents. We therefore undertook this study to determine (1) the apoptotic pathway of anulus fibrosus cells and (2) the anti-apoptotic potential of caspase inhibitors. METHODS: Rat anulus fibrosus cells were isolated, cultured, and placed in either 0% (apoptosis-promoting condition) or 10% (normal control) fetal bovine serum. We identified and quantified the presence of apoptotic cell death, caspase activities, and loss of mitochondrial membrane potential. In addition, we examined the cells for the expression of Fas, procaspases, and cytochrome-c. Finally, we analyzed the degree of anti-apoptotic effects of caspase inhibitors on the cells in 1% fetal bovine serum. RESULTS: The percentage of apoptosis and Fas expression in the cells incubated in 0% fetal bovine serum were increased compared with those in the cells incubated in 10% fetal bovine serum (both p < 0.001). Caspase-8, 9, and 3 activities were increased and expression of procaspases was decreased in the 0% fetal bovine serum compared with those in the 10% fetal bovine serum (all p < 0.001). In contrast, the loss of mitochondrial membrane potential and cytochrome-c release into the cytosol were unchanged in the 0% fetal bovine serum. Pancaspase and caspase-8 inhibitors reduced apoptotic cell death (p < 0.001 and p < 0.05, respectively), but caspase-9 inhibitor did not reduce apoptotic cell death. CONCLUSIONS: Our results suggest that, unlike nucleus pulposus cells, anulus fibrosus cells are Fas Type-I cells, which undergo apoptosis through the death-inducing signaling complex. We also found that apoptosis of intervertebral disc cells can be attenuated by caspase inhibitors.     

Needle puncture injury of the rat intervertebral disc affects torsional and compressive biomechanics differently

Needle puncture is a common method of inducing intervertebral disc (IVD) degeneration in small animal models and may have some similarities to IVD injury conditions such as herniation. Yet, the influence of puncture injuries on IVD biomechanics is not well understood. This study quantified the acute effects of anular injury on the biomechanics of rat caudal IVDs in compression and torsion following puncture with 30, 25 and 21 G needles. In compression, puncture injury reduced elastic stiffness by 20% for all needle sizes, but differences between control and punctured discs did not remain after compressive overload. In contrast, torsional parameters associated with anular fiber tension were affected proportionally with needle size. We conclude that IVD injuries that penetrate through the thickness of the annulus affect IVD biomechanics through different mechanisms for compression and torsion. Anular injuries affect torsional properties in a manner directly related to the amount of fiber disruption and compressive properties in a manner that affects pressurization.     

Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro

STUDY DESIGN: Human cells from the anulus were grown in tissue culture in an experimental design to study the anti-apoptotic effect of two selected cytokines. OBJECTIVES: To determine whether two selected cytokines, insulin-like growth factor-1 and platelet-derived growth factor, were effective in decreasing apoptosis in human cells from the anulus grown in culture for 10 days. SUMMARY OF THE BACKGROUND DATA: Previous studies have shown that there is a small cell population in the aging human intervertebral disc. Earlier work from the authors' laboratory suggested that apoptosis (programmed cell death) may be a major contributing factor to the decrease in cell number. A wide variety of inhibitors of apoptosis have now been identified; the present report presents findings on the actions of insulin-like growth factor-1 and platelet-derived growth factor in retarding or preventing apoptosis. METHODS: Using previously published culture methods, cells from the anulus of 25 subjects (mean age, 41.7 years) were grown in monolayer culture for 10 days and tested under the following conditions: 1) control growth in the presence of 20% fetal bovine serum; 2) positive control conditions promoting the development of apoptosis in the absence of serum; or 3) in dose-response regimes where insulin-like growth factor-1 or platelet-derived growth factor were added in the presence of only 1% fetal bovine serum (necessary for basal cell maintenance). Specimens were derived from 18 lumbar, 9 cervical, and 1 thoracic sites; the average Thompson score was III. Cells were grown on chambered slides and evaluated in situ using the TdT in situ apoptosis detection reaction to identify apoptotic cells. An average of 300 cells were counted in replicate cultures at each dose to determine the incidence of apoptosis; results were analyzed with standard statistical techniques. Cultured cells also were examined with transmission electron microscopy. RESULTS: Serum withdrawal to a 1% level was used as a positive apoptosis control in vitro and resulted in a significantly greater percentage of apoptosis compared with the 20% serum negative control (1.02% +/- 0.34 (28) versus 0.14% +/- 0. 04 (27; mean +/- SEM (n)), P < 0.0001). Exposure to 50 ng/mL insulin-like growth factor-1 significantly reduced the percentage of apoptosis (vs.- 1% serum) to 0.49% +/- 0.26 (P = 0.005); 500 ng/mL was also significantly effective (% apoptosis = 0.09% +/- 0.04 (P = 0.0001). Platelet-derived growth factor at a dose of 100 ng/mL also significantly reduced apoptosis (0.18 +/- 0.11, P = 0.0001). CONCLUSIONS: Data demonstrate a significant reduction in the percentage of apoptotic disc cells after exposure to 50-500 ng/mL insulin-like growth factor-1 or exposure to 100 ng/mL platelet-derived growth factor. These findings expand the understanding of the cell biology of the disc cell and show that selected cytokines can retard or prevent programmed cell death in vitro. The administration of these cytokines may have future therapeutic potential in the treatment of disc degeneration.     

力学载荷与椎间盘退变关系的研究进展

力学载荷是维持椎间盘细胞及基质的生物代谢的重要因素.椎间盘是人体内最大的无血管组织,椎间盘与周围组织的营养物质以及代谢产物的交换主要通过弥散与对流,组织间隙压力平衡的变化与渗透压的改变,为生长因子、细胞因子及酶类的运转提供泵效应[1].椎间盘内压力变化与机体昼夜的活动有关,直立位与负重状态下对椎间盘产生较高压力载荷,而卧位时椎间盘承受的压力较小[2].椎间盘在高压力载荷状态下产生形变,内部静水压升高,水分被缓慢挤出.     

Effects of compressive loading on biomechanical properties of disc and peripheral tissue in a rat tail model

Intervertebral disc degeneration induced by mechanical compression is an important issue in spinal disorder research. In this study, the biomechanical aspect of the rat tail model was investigated. An external loading device equipped with super-elastic TiNi springs was developed to apply a precise load to the rat tail. By using this device, rat tail discs were subjected to compressive stress of 0.5 or 1.0 MPa for 2 weeks. Discs in the sham group received an attachment of the device but no loading. After the experimental period, first the intact tail with peripheral tissues (PT) such as tendon and skin and then the retrieved disc without PT were subjected to a uniaxial tension–compression test; biomechanical characteristics such as range of motion (ROM), neutral zone (NZ), and hysteresis loss (HL) were evaluated. Furthermore, the load-bearing contribution of PT in the intact tail was estimated by comparing the load–displacement curves obtained by the mechanical tests performed with and without PT. The experimental findings revealed that the continuous compressive stress induced reduction in disc thickness. The intact tail demonstrated decreases in ROM and NZ as well as increases in HL. On the other hand, the retrieved disc demonstrated increases in ROM, NZ, and HL. Further, a significant increase in the load-bearing contribution of PT was indicated. These findings suggest that the load-bearing capacity of the disc was seriously deteriorated by the application of compressive stress of 0.5 or 1.0 MPa for 2 weeks.     

Effect of intervertebral disc height on postoperative motion and clinical outcomes after Prodisc-C cervical disc replacement

Background contextCervical total disc replacement (TDR) is an emerging technology. However, the factors that influence postoperative range of motion (ROM) and patient satisfaction are not fully understood.PurposeTo evaluate the influence of pre- and postoperative disc height on postoperative motion and clinical outcomes.Study design/settingRetrospective review of patients enrolled in prospective randomized Food and Drug Administration (FDA) trial.Patient sampleOne hundred sixty-six patients with single-level ProDisc-C arthroplasty performed were evaluated.Outcome measuresROM and clinical outcomes based on Neck Disability Index (NDI) and Visual Analog Scale (VAS) were assessed.MethodsPreoperative and postoperative disc height and ROM were measured from lateral and flexion-extension radiographs. Student t test and Spearman's rho tests were performed to determine any correlation or “threshold” effect between the disc height and ROM or clinical outcome.ResultsPatients with less than 4 mm of preoperative disc height had a mean 1.8° increase in flexion-extension ROM after TDR, whereas patients with greater than 4 mm of preoperative disc height had no change (mean, 0°) in flexion-extension ROM (p=.04). Patients with greater than 5 mm of postoperative disc height have significantly higher postoperative flexion-extension ROM (mean, 10.1°) than those with less than 5 mm disc height (mean, 8.3°, p=.014). However, patients with greater than 7 mm of postoperative disc height have significantly lower postoperative lateral bending ROM (mean, 4.1°) than those with less than 7 mm disc height (mean, 5.7°, p=.04). It appears that the optimal postoperative disc height is between 5 and 7 mm for increased ROM on flexion extension and lateral bending. There was a mean improvement of 30.5 points for NDI, 4.3 points for VAS neck pain score, and 3.9 points for VAS arm pain score (all p<.001). No correlation could be found between clinical outcomes and disc height. Similarly, no threshold effect could be found between any specific disc height and NDI or VAS.ConclusionPatients with greater disc collapse of less than 4 mm preoperative disc height benefit more in ROM after TDR. The optimal postoperative disc height range to maximize ROM is between 5 and 7 mm. This optimal range did not translate into better clinical outcome at 2-year follow-up.     

Quantitative assessment of abdominal aortic calcification and associations with lumbar intervertebral disc height loss: the Framingham Study

Background contextVascular disease has been proposed as a risk factor for disc height loss (DHL).PurposeTo examine the relationship between quantitative measures of abdominal aortic calcifications (AACs) as a marker of vascular disease, and DHL, on computed tomography (CT).Study designCross-sectional study in a community-based population.Patient sampleFour hundred thirty-five participants from the Framingham Heart Study.Outcome measuresQuantitative AAC scores assessed by CT were grouped as tertiles of “no” (reference), “low,” and “high” calcification. Disc height loss was evaluated on CT reformations using a four-grade scale. For analytic purposes, DHL was dichotomized as moderate DHL of at least one level at L2–S1 versus less than moderate or no DHL.MethodsWe examined the association of AAC and DHL using logistic regression before and after adjusting for cardiovascular risk factors and before and after adjusting for age, sex, and body mass index (BMI).ResultsIn crude analyses, low AAC (odds ratio [OR], 2.05 [1.27–3.30]; p=.003) and high AAC (OR, 2.24 [1.38–3.62]; p=.001) were strongly associated with DHL, when compared with the reference group of no AAC. Diabetes, hypercholesterolemia, hypertension, and smoking were not associated with DHL and did not attenuate the observed relationship between AAC and DHL. Adjustment for age, sex, and BMI markedly attenuated the associations between DHL and low AAC (OR, 1.20 [0.69–2.09]; p=.51) and high AAC (OR, 0.74 [0.36–1.53]; p=.42).ConclusionsAbdominal aortic calcification was associated with DHL in this community-based population. This relationship was independent of cardiovascular risk factors. However, the association of AAC with DHL was explained by the effects of age, sex, and BMI.     

辛伐他汀对兔髓核细胞的影响

目的 观察辛伐他汀对兔髓核细胞Ⅱ型胶原(ColⅡ)及聚集蛋白聚糖(Agg)表达的影响.方法 取兔髓核细胞进行原代培养,传至第3代行ColⅡ免疫组织化学鉴定后随机分为5组,以不同浓度辛伐他汀处理:A组:空白对照组;B、C、D、E组分别为0.1、0.2、0.4、0.8 μmol/L辛伐他汀组.运用半定量逆转录-聚合酶链反应(RT-PCR)检测ColⅡ、Agg含量的变化,并行细胞活力检测.结果 辛伐他汀浓度超过0.2 μmol/L时ColⅡ及Agg的表达增加,0.4 μmoL/L时达到高峰(P＜0.05),0.8 μmol/L时ColⅡ及Agg表达下降.0.8 μmol/L处理组影响细胞活力,0.1～0.4 μmol/L范围时细胞活性无明显影响(P＜0.05).结论 辛伐他汀可促进兔髓核细胞ColⅡ及Agg的表达,改善椎间盘退变进程;在＜0.4 μmol/L的较低浓度内对细胞活力无明显影响.     

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。