Spaceflight‐induced bone loss alters failure mode and reduces bending strength in murine spinal segments

Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30‐day Bion M1 mission and eight vivarium controls were loaded to failure in four‐point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro‐computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force‐displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc‐vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:48–57, 2016.     

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     

Endplate deflection is a defining feature of vertebral fracture and is associated with properties of the underlying trabecular bone

Endplate deflection frequently occurs with vertebral failure, but the relationship between the two remains poorly defined. This study examined associations between endplate deflection under compressive loading and characteristics of the neighboring subchondral bone and intervertebral disc (IVD). Ten L1 vertebrae with adjacent IVDs were dissected, compressed axially in a stepwise manner to failure, and imaged with micro‐computed tomography before each loading step. From the images, deflection was measured across the surface of each endplate at each step. Trabecular microstructure and endplate volume fraction were evaluated in 5 mm regions just under the superior endplate. IVDs were assessed using computed tomography and histology. A marked increase in superior endplate deflection coincided with a drop in the load‐displacement curve. Endplate deflection was higher in regions with less robust bone microstructure (p < 0.009), though these associations tended to weaken as loading progressed. Immediately following the ultimate point, endplate deflection was higher in regions underlying the nucleus pulposus versus annulus fibrosus (p = 0.035), irrespective of disc grade (p = 0.346). These results indicate that a sudden increase in endplate deflection signals that the mechanical competence of the vertebra has been compromised. The mechanisms of endplate failure likely relate to anatomical features of the endplate, neighboring trabecular bone, and IVD. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:880–886, 2014.     

Lumbar spine endplate fractures: Biomechanical evaluation and clinical considerations through experimental induction of injury

Lumbar endplate fractures were investigated in different experimental scenarios, however the biomechanical effect of segmental alignment was not outlined. The objectives of this study were to quantify effects of spinal orientation on lumbar spine injuries during single‐cycle compressive loads and understand lumbar spine endplate injury tolerance. Twenty lumbar motion segments were compressed to failure. Two methods were used in the preparation of the lumbar motion segments. Group 1 (n = 7) preparation maintained pre‐test sagittal lordosis, whereas Group 2 (n = 13) specimens had a free‐rotational end condition for the cranial vertebra, allowing sagittal rotation of the cranial vertebra to create parallel endplates. Five Group 1 specimens experienced posterior vertebral body fracture prior to endplate fracture, whereas two sustained endplate fracture only. Group 2 specimens sustained isolated endplate fractures. Group 2 fractures occurred at approximately 41% of the axial force required for Group 1 fracture (p < 0.05). Imaging and specimen dissection indicate endplate injury consistently took place within the confines of the endplate boundaries, away from the vertebral periphery. These findings indicate that spinal alignment during compressive loading influences the resulting injury pattern. This investigation identified the specific mechanical conditions under which an endplate breach will take place. Development of endplate injuries has significant clinical implication as previous research identified internal disc disruption (IDD) and degenerative disc disease (DDD) as long‐term consequences of the axial load‐shift that occurs following a breach of the endplate. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1084–1091, 2016.     

Microstructural analysis of three‐dimensional canal network in the rabbit lumbar vertebral endplate

Insufficient nutrient supply through vertebral canal structures to the intervertebral disc (IVD) has been considered as an important contributor for disc degeneration. Despite previous canal structure characterization studies using histology, scanning electron microscopy, and angiography, among others, their three‐dimensional (3D) topology inside the vertebral endplate remains poorly understood. This study aims to characterize the 3D canal structure in the rabbit lumbar vertebral endplate using micro computed tomography (μCT). Vertebral endplates were imaged using high‐resolution μCT with 1.4 × 1.4 × 1.8 μm voxel size. Diameter, length, orientation, and depth starting from the vertebral endplate surface were analyzed for each canal using individual 3D canal models from the vertebral endplate scans. In the layer underneath the vertebral endplate, at a mean depth of 76.2 μm, longitudinally‐oriented relatively short‐length (57.6 μm) and small diameter (45.7 μm) canals were dominant. Large‐scale canals with a mean diameter of 152.1 μm running parallel to the endplate surface were isolated at the depth of 224.1 μm. These canals were connected to both IVD and bone marrow spaces through vertically oriented canals. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:270–276, 2015.     

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.     

High glucose‐induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells

Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high‐glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha‐lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bcl‐2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose‐ and time‐dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but decreased the level of the anti‐apoptotic protein Bcl‐2. ALA inhibited the expression of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but enhanced the expression of Bcl‐2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose‐induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose‐ and time‐dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2476–2483, 2018.

     

Evaluation of intervertebral disc cartilaginous endplate structure using magnetic resonance imaging

Purpose

The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage positioned between the vertebral endplate and nucleus pulposus (NP) that functions both as a mechanical barrier and as a gateway for nutrient transport into the disc. Despite its critical role in disc nutrition and degeneration, the morphology of the CEP has not been well characterized. The objective of this study was to visualize and report observations of the CEP three-dimensional morphology, and quantify CEP thickness using an MRI FLASH (fast low-angle shot) pulse sequence.

Methods

MR imaging of ex vivo human cadaveric lumbar spine segments (N = 17) was performed in a 7T MRI scanner with sequence parameters that were selected by utilizing high-resolution T1 mapping, and an analytical MRI signal model to optimize image contrast between CEP and NP. The CEP thickness at five locations along the mid-sagittal AP direction (center, 5 mm, 10 mm off-center towards anterior and posterior) was measured, and analyzed using two-way ANOVA and a post hoc Bonferonni test. For further investigation, six in vivo volunteers were imaged with a similar sequence in a 3T MRI scanner. In addition, decalcified and undecalcified histology was performed, which confirmed that the FLASH sequence successfully detected the CEP.

Results

CEP thickness determined by MRI in the mid-sagittal plane across all lumbar disc levels and locations was 0.77 ± 0.24 mm ex vivo. The CEP thickness was not different across disc levels, but was thinner toward the center of the disc.

Conclusions

This study demonstrates the potential of MRI FLASH imaging for structural quantification of the CEP geometry, which may be developed as a technique to evaluate changes in the CEP with disc degeneration in future applications.     

Cartilage‐on‐cartilage versus metal‐on‐cartilage impact characteristics and responses

A common in vitro model for studying acute mechanical damage in cartilage is to impact an isolated osteochondral or cartilage specimen with a metallic impactor. The mechanics of a cartilage‐on‐cartilage (COC) impact, as encountered in vivo, are likely different than those of a metal‐on‐cartilage (MOC) impact. The hypothesis of this study was that impacted in vitro COC and MOC specimens would differ in their impact behavior, mechanical properties, chondrocyte viability, cell metabolism, and histologic structural damage. Osteochondral specimens were impacted with either an osteochondral plug or a metallic cylinder at the same delivered impact energy per unit area, and processed after 14 days in culture. The COC impacts resulted in about half of the impact maximum stress and a quarter of the impact maximum stress rate of change, as compared to the MOC impacts. The impacted COC specimens had smaller changes in mechanical properties, smaller decreases in chondrocyte viability, higher total proteoglycan content, and less histologic structural damage, as compared to the impacted MOC specimens. If MOC impact conditions are to be used for modeling of articular injuries and post‐traumatic osteoarthritis, the differences between COC and MOC impacts must be kept in mind. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 887–893, 2013     

Low‐intensity pulsed ultrasound stimulation enhances TIMP‐1 in nucleus pulposus cells and MCP‐1 in macrophages in the rat

Recent studies have reported that low‐intensity pulsed ultrasound (LIPUS) stimulates cell proliferation and proteoglycan production in rabbit intervertebral disc cells, and moreover promotes the secretion of MCP‐1 (monocyte chemotaxis protein‐1) from macrophages in a disc organ culture model. These findings suggest the possible application of LIPUS for biological repair of disc degeneration and herniation. Although the mechanisms involved are not well understood, several cytokine pathways may play a role. Therefore, in order to evaluate the effect of LIPUS stimulation on cytokine production by nucleus pulposus cells and macrophages, in vitro culture studies were designed. Nucleus pulposus cells and macrophages were collected from Sprague‐Dawley rats, cultured separately in a monolayer, and stimulated with LIPUS for 7 days. After culture, the culture medium and the cells were analyzed by cytokine array, RT‐PCR, and ELISA. Cytokine array showed that LIPUS stimulation significantly upregulated TIMP‐1 (tissue inhibitor of metalloproteinase‐1) in the nucleus pulposus and MCP‐1 in macrophages in comparison with the control. This was confirmed at the gene level by RT‐PCR in nucleus pulposus cells and macrophages after stimulation with LIPUS. Quantitative evaluation of these proteins by ELISA showed higher levels in nucleus pulposus cells and macrophages stimulated by LIPUS than in controls. These results showed that LIPUS stimulation significantly activated TIMP‐1 and MCP‐1 in nucleus pulposus cells and macrophages at both the protein and gene levels, suggesting that LIPUS may be a promising supplemental treatment for intervertebral disc herniation. © 2008 Orthopaedic Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:865–871, 2008     

Scheuermann's disease: An update

Scheuermann's disease is a juvenile osteochondrosis of the spine. It is a disease of the growth cartilage endplate, probably due to repetitive strain on the growth cartilage weakened by a genetic background. The radiographic aspects are related to the vertebral endplate lesions and include vertebral wedging, irregularity of the vertebral endplate, and Schmorl's node (intraossous disk herniation). Disc alterations are frequent and may be secondary to dysfunction of the disc–vertebra complex. The definitions of Scheuermann's disease are varied; it can refer to the classical form of juvenile kyphosis, described by Scheuermann as well as asymptomatic radiographic abnormalities. Lumbar involvement is probably as frequent as the thoracic form and might be more painful. The first-line treatment is medical and includes rehabilitation and bracing. The earlier the start of treatment, the better the outcome, which highlights the importance of early diagnosis. Surgery is uncommon and must be limited to severe involvement after failure of conservative treatment. The natural history of Scheuermann's disease is unknown, but it might be associated with increased risk of back pain. The evolution of thoracolumbar and lumbar disease is unknown.     

Glenoid loosening after total shoulder arthroplasty: An in vitro CT‐scan study

Glenoid fixation failure has only been grossly characterized. This lack of information hinders attempts to improve fixation because of a lack of methodologies for detecting and monitoring fixation failure. Our goal was twofold: to collect detailed data of glenoid fixation fracture, and to investigate computed tomography (CT)‐scanning as a tool for investigations of fixation failure. Six cadaver scapulas and six bone‐substitute specimens were cyclically loaded and CT‐scanned at clinical settings after 0, 1,000, 5,000, 10,000, 30,000, 50,000 and 70,000 load cycles. The fixation status was evaluated by inspection of the scans. After 70,000 cycles, the specimens were sectioned, and the fixation inspected by microscopy. The results of the microscopy analysis were compared to the CT‐scan analysis. Fracture of the glenoid fixation initiated at the edge of the glenoid rim and propagated towards and around the keel of the implant. The entire process from initiation to complete fracture took place at the polyethylene implant–cement interface, while the cement, the adjacent bone, and the cement–bone interface remained intact. Thus, strengthening the polyethylene–cement interface should improve glenoid fixation. Microscopy results validated the CT methodology, suggesting that the CT technique is reliable. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1589–1595, 2009     

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.     

Altered disc pressure profile after an osteoporotic vertebral fracture is a risk factor for adjacent vertebral body fracture

This study investigated the effect of endplate deformity after an osteoporotic vertebral fracture in increasing the risk for adjacent vertebral fractures. Eight human lower thoracic or thoracolumbar specimens, each consisting of five vertebrae were used. To selectively fracture one of the endplates of the middle VB of each specimen a void was created under the target endplate and the specimen was flexed and compressed until failure. The fractured vertebra was subjected to spinal extension under 150 N preload that restored the anterior wall height and vertebral kyphosis, while the fractured endplate remained significantly depressed. The VB was filled with cement to stabilize the fracture, after complete evacuation of its trabecular content to ensure similar cement distribution under both the endplates. Specimens were tested in flexion-extension under 400 N preload while pressure in the discs and strain at the anterior wall of the adjacent vertebrae were recorded. Disc pressure in the intact specimens increased during flexion by 26 ± 14%. After cementation, disc pressure increased during flexion by 15 ± 11% in the discs with un-fractured endplates, while decreased by 19 ± 26.7% in the discs with the fractured endplates. During flexion, the compressive strain at the anterior wall of the vertebra next to the fractured endplate increased by 94 ± 23% compared to intact status (p < 0.05), while it did not significantly change at the vertebra next to the un-fractured endplate (18.2 ± 7.1%, p > 0.05). Subsequent flexion with compression to failure resulted in adjacent fracture close to the fractured endplate in six specimens and in a non-adjacent fracture in one specimen, while one specimen had no adjacent fractures. Depression of the fractured endplate alters the pressure profile of the damaged disc resulting in increased compressive loading of the anterior wall of adjacent vertebra that predisposes it to wedge fracture. This data suggests that correction of endplate deformity may play a role in reducing the risk of adjacent fractures.     

Construct damage and loosening around glenoid implants: A longitudinal micro‐CT study of five cadaver specimens

The evolution of failure of bone and cement leading to loosening of glenoid components following shoulder arthroplasty is not well understood. The purpose of this study was to identify and visualize potential mechanisms of mechanical failure within cadavers, cemented with two types of components, and subject to cyclic loading. Five glenoid cadaver bones were implanted with either a three‐pegged polyethylene component, or prototype posteriorly augmented component which addresses posterior bone loss. Specimens were loaded by constant glenohumeral compression combined with cyclic anterior–posterior displacement of the humeral head relative to the glenoid. At six time points across 100,000 cycles, implant loosening micromotions were optically measured, and specimens were imaged by micro‐computed tomography. Scans were 3D registered and inspected for crack initiation and progression, and micro‐CT based time‐lapse movies were created. Cement cracking initiated at stress concentrations and progressed with additional cyclic loading. Failure planes within trabecular bone and the bone–cement interface were identified in four of the five specimens. Implant subsidence increased to greater than 1.0 mm in two specimens. Cemented glenoid structural failure can occur within the cement, along planes of trabecular bone, or at the bone cement interface. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1053–1060, 2016.     

Correlations between effective permeability and marrow contact channels surface of vertebral endplates

Homeostasis of the intervertebral disc relies on nutrient supply and waste clearance through the dense capillary network that is in contact with the cartilage endplate (CEP). We developed a micro‐computerized tomography (micro‐CT) method to quantify the marrow contact channel surface (MCCS) with the CEP and to validate the hypothesis according to which MCCS was correlated to the effective permeability of the vertebral endplate (VEP) and influenced by the mechanical stimuli. The influence of compression loading on local vascularization was investigated. Six 4‐week‐old skeletally immature pigs were instrumented with left pedicle screws and rod at both T5–T6 and L1–L2 levels to create asymmetrical spine tethers. After 3 months of growth, three cylindrical specimens of the VEP (one central and two lateral right and left) were obtained from both the instrumented and the control levels. We used a previously validated method for measuring permeability. Micro‐CT analysis (resolution 12 µm) yielded a gray‐scale 2D‐image of the discal end of each specimen converted into a binary 2D‐image to derive the MCCS. Correlations between MCCS and effective permeability were assessed. Effective permeability and MCCS were significantly decreased compared to the control group especially on the tethered side (?41.5%, p = 0.004 and ?52.5%, p = 0.0009, respectively). Correlations were significant and showed maximal value (r² = 0.430, p < 0.0001) on the tethered side involving maximal compressive loadings. Mechanical stimuli, due to unbalanced growth, altered the vascularization and the convective properties of the CEP. The cascade of mechanobiological events should offer perspectives for research on disc degeneration and attempted treatment. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1229–1234, 2010     

Interleukin‐6 and interleukin‐6 receptor expression,localization, and involvement in pain‐sensing neuron activation in a mouse intervertebral disc injury model

The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain‐related mediators, such as interleukin‐6 (IL‐6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL‐6 and IL‐6 receptor (IL‐6R) expression after IVD injury as well as determine the involvement of IL‐6/IL‐6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL‐6 and IL‐6R in IVDs by enzyme‐linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL‐6 inhibitor by evaluating pain‐related protein, calcitonin gene‐related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL‐6 and IL‐6R. IL‐6 and IL‐6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL‐6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL‐6 and IL‐6R expression levels are responsive to IVD injury and that inhibition of IL‐6/IL‐6R signaling may be a promising analgesic treatment for degenerative disc diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1508–1514, 2015.     

腰骶部移行椎与腰椎间盘突出症的关系探讨

目的探讨腰骶部移行椎与腰椎间盘突出症的关系。方法将因非椎间盘突出症原因而行腰椎X线片检查的104例患者设为对照组;经手术证实腰椎间盘突出的91例患者设为腰椎间盘突出症组。比较两组患者的腰椎正位X线片,统计两组患者腰骶部移行椎发生率的差异及与移行椎与腰椎间盘突出部位的关系。结果对照组腰骶部移行椎发生率为18．3％,腰椎间盘突出症组为52．7％,两组间差异有统计学意义。腰椎间盘突出症组中合并移行椎者椎间盘突出发生于移行椎上一间隙者为58．3％;单侧移行椎椎间盘突出发生在移行椎畸形同侧者占75．9％,其中在移行椎上一间隙者占81．8％;发生在移行椎畸形对侧者占17．2％,其中在其下一间隙者占80．0％。结论腰骶部移行椎与腰椎间盘突出症有着密切关系,是诱发腰椎间盘突出症的重要危险因素之一。     

Long‐Term Pathology of Ovine Lumbar Spine Degeneration Following Injury Via Percutaneous Minimally Invasive Partial Nucleotomy

The focus of this work is to assess the long‐term progression of degeneration in the ovine lumbar spine following a minimally invasive model injury comparable to the damage of an intervertebral disc (IVD) herniation. A partial nucleotomy was performed on 18 sheep via the percutaneous dorsolateral approach. The animals were culled at 6 and 12 months to evaluate the damaged and neighboring functional spine units (FSUs) for degenerative characteristics via μ‐CT and histology. Both quantitative μ‐CT and histology investigations demonstrated statistically significant differences between the native and damaged FSUs investigated. Qualitative analysis of μ‐CT revealed numerous pathological markers consistent with intervertebral disc degeneration (IDD), with differences in frequency and severity between the native and damaged FSUs. The annulus fibrosus reforms a pressure seal within 6 weeks, but the extent of the trauma is significant enough to initiate IVD degeneration, which is already clearly visible at 6 months and especially so 12 months post‐op. IDD pathology consistent with signs of a herniation was seen in both the 6‐ and 12‐month groups. This technique provides a useful model injury for the preclinical evaluation of IDD in large animal models, especially in regards to simulating disc herniation as well as for testing the efficacy of associated therapies in the future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2376–2388, 2019     

Exposure of the porcine spine to mechanical compression: differences in injury pattern between adolescents and adults

Recent studies of the spine in adolescents who have sustained trauma have shown injuries to the growth zone, whereas injuries to the vertebral body have been described in other studies of only adults. There are also reports on different clinical signs and radiological findings in adolescents with lumbar disc herniation when compared to adults. In order to find an explanation for these differences between adolescents and adults, this experimental study was performed. Six cadaveric lumbar motion segments (vertebral body-disc-vertebral body) obtained from three young male pigs and six lumbar motion segments obtained from three mature male pigs were tested in axial compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histological samples were taken from the injury site. In the adolescents, a fracture was consistently found in the endplate through the posterior part of the growth zone, displacing the anulus fibrosus with a bony fragment at the point of insertion to the vertebra. This type of injury could not be detected in any of the adults; instead, there was a fracture of the vertebra in four cases, and in two cases, a rupture of the anulus fibrosus without a bony fragment was seen. This study showed that, when compressed to failure, the weakest part of the lumbar spine of the adolescent pig differs from that of the mature pig in the same way that studies on human spinal units have shown. Received: 18 November 1999 Revised: 2 March 2000 Accepted: 30 March 2000