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Lumbar spinal stenosis (LSS) is a condition wherein patients exhibit age-related fibrosis, elastin-to-collagen ratio reductions, and ligamentum flavum hypertrophy. This study was designed to assess the relationship between SIRT6 and telomerase activity in hypertrophic ligamentum flavum (LFH) cells from LSS patients. We observed significant reductions in SIRT6, TPP1, and POT1 protein levels as well as increases in telomerase reverse transcriptase (TERT) levels and telomerase activity in LFH tissues relative to non- hypertrophic ligamentum flavum (LFN) tissues. When SIRT6 was overexpressed in these LFH cells, this was associated with significant increases in telomerase activity and a significant reduction in fibrosis-related protein expression. These effects were reversed, however, when telomerase activity was inactivated by hTERT knockdown in these same cells. SIRT6 overexpression was further found to reduce the frequency of senescence-associated β-galactosidase (SA-β-Gal)-positive LFH cells and to decrease p16, MMP3, and L1 mRNA levels and telomere dysfunction-induced foci (TIFs) in LFH cells. In contrast, hTERT knockdown-induced telomerase inactivation eliminated these SIRT6-dependent effects. Overall, our results indicate that SIRT6 functions as a key protective factor that prevents cellular senescence and telomere dysfunction in ligamentum flavum cells, with this effect being at least partially attributable to SIRT6-dependent telomerase activation.

STUDY DESIGN Sequencing and experimental analysis of the expression profile of circular RNAs (circRNAs) in hypertrophic ligamentum flavum (LFH). OBJECTIVES The aim of this study was to identify differentially expressed circRNAs between LFH and nonhypertrophic ligamentum flavum tissues from lumbar spinal stenosis (LSS) patients. SUMMARY OF BACKGROUND DATA Hypertrophy of the ligamentum flavum (LF) can cause LSS. circRNAs are important in various diseases. However, no circRNA expression patterns related to LF hypertrophy have been reported. METHODS A total of 33 patients with LSS participated in this study. LF tissue samples were obtained when patients underwent decompressive laminectomy during surgery. The expression profile of circRNAs was analyzed by transcriptome high-throughput sequencing and validated with quantitative real-time polymerase chain reaction (PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for the differentially expressed circRNA-associated genes and related pathways. The connections between circRNAs and microRNAs were explored using Cytoscape. The role of hsa_circ_0052318 on LF cell fibrosis was assessed by analyzing the expression of collagen I and collagen III. RESULTS The results showed that 2439 circRNAs of 4025 were differentially expressed between the LFH and nonhypertrophic ligamentum flavum tissues, including 1276 upregulated and 1163 downregulated circRNAs. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these differentially expressed circRNAs functioned in biological processes, cellular components, and molecular functions. Autophagy and mammalian target of rapamycin were the top two signaling pathways affected by these circRNAs. Five circRNAs (hsa_circ_0021604, hsa_circ_0025489, hsa_circ_0002599, hsa_circ_0052318, and hsa_circ_0003609) were confirmed by quantitative real-time PCR. The network indicated a strong relationship between circRNAs and miRNAs. Furthermore, hsa_circ_0052318 overexpression decreased mRNA and protein expression of collagen I and III in LF cells from LFH tissues. CONCLUSION This study identified circRNA expression profiles characteristic of hypertrophied LF in LSS patients, and demonstrated that hsa_circ_0052318 may play an important role in the pathogenesis of LF hypertrophy.Level of Evidence: N/A.

Objective: This study was designed to investigate the relationship between the laminar slope angle (LSA) and the lumbar disc degenerative grade, the cross-section area (CSA) of multifidus muscle, the muscle-fat index, and the thickness of the ligamentum flavum. Methods: Retrospective analysis of 122 patients who were scheduled to undergo a lumbar operation for diagnoses associated with degenerative lumbar disease between January and December 2017. The L4–L5 disc grade was evaluated from preoperative sagittal T2-weighed magnetic resonance imaging of the lumber region; the CSA of the multifidus and muscle-fat index were measured at the L4 level, while the thickness of the ligamentum flavum was measured at the L4–L5 facet level from axis T2-weighed magnetic resonance imaging. The slope of the laminar was evaluated from preoperative three-dimensional computer tomography at the tip level of the facet joints and selected by the axis plane. Independent-sample T-tests were used to assess the association between age and measurement indices. Results: Our results showed that age was positively connected with the LSA of L4 and L5 in different patients, although there was no significant difference between age and the difference of the two segment LSA. Partial correlation analysis, excluding the interference of age, revealed a strong negative relationship between the LSA of L4 and the thickness of the ligamentum flavum, irrespective of whether we considered the left or right. However, there was no correlation with lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. Conclusion: The thickness of the ligamentum flavum showed changes with anatomical differences in the LSA, but not the lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. A small change in LSA may cause large mechanical stress; this may be one of the causative factors responsible for lumbar spinal stenosis.

The present study aimed to investigate the association between the serum SIRT1 protein and the severity of spinal cord injury (SCI) as well as the neurological recovery in mice. In this study, the wild-type (WT), Mx1-Cre+ SIRT1loxP/loxP (Mx1), and LCK-Cre+SIRT1loxP/loxP (LCK) mice were subjected to sham surgery, mild, moderate, or severe SCI, respectively. The serum was collected at intervals of 12 h, 1 day (d), 3 d, 5 d, 7 d, 10 d, 14 d, and 21 d after the injury. The locomotor function of all the animals was assessed using the Basso mouse scale (BMS) and the serum SIRT1 proteins were analyzed using enzyme-linked immunosorbent assay (ELISA). The results demonstrated that about 7–10 d after SCI, the levels of SIRT1 protein in the serum correlated significantly with the severity of the injury and at 28 d post-injury, there was a distant neurological recovery (BMS score). The serum SIRT1 concentration in both the Mx1 and LCK mice in the sham group was significantly reduced compared to that in the WT mice, and there was a delayed increase in the serum SIRT1 levels after injury. These findings indicate that the SIRT1 concentrations in the serum of the SCI mice closely correlated with the acute severity and neurological outcome.

Background.One previous work confirmed that laminar slope angle was associated with the ossification of thoracic ligamentum flavum. Several studies have investigated the relevance of disc degeneration grade, thickness of ligamentum flavum, along with cross section area of multifidus and its fatty infiltration. However, there has been no research between the angle and them. This retrospectivestudyof clinical materials from 122 patients was designed to investigate the influence of laminar slope angle on degeneration of lumbar when eliminating the interference of age.Methods.122 individuals were retrospected randomly on the basis of age difference from 687inpatients scheduled to undergo a lumbar operation between January and December 2017.We registered their age and sex, evaluated and measuredL4-L5 disc degeneration grade,correspondingcross section area of multifidus, muscle-fat index,thickness of ligamentum flavum and laminar slope angle from preoperative magnetic resonance imagingand three-dimensional computer tomography. Independent-sample T tests were used to assess the association between age and measurement indices. The Pearson correlation coefficient, and partial correlation excluding age, was also performed to analyze thecorrelation between clinical parameters.Results.Our results showed that age was positively connected withthe laminar slope angle(L4:r=0.298, p=＜0.01; L5:r=0.303, p=＜0.01). Excluding the interference of age, revealed a credibly negative relationship between the angle of L4 and the thickness of the ligamentum flavum(Left: r=-0.303, p=＜0.01;Right:r=-0.340, p=＜0.01). However, there was no correlationwithother parameters(disc: r=-0.141, p＞0.05; left multifidus: r=0.248, p＞0.05; right multifidus: r=0.225, p＞0.05; left muscle-fat index: r=0.033, p＞0.05; right muscle-fat index: r=0.016, p＞0.05).Conclusion.Excluding the interference of age, Inclination of small laminar slope angle leads to hypertrophy of lumbar ligamentum flavum.LEVEL OF EVIDENCE:Level 4.

Longitudinal bone growth is governed by a complex network of endocrine signals including leptin. In mouse, leptin deficiency leads to distinct phenotypes in bones of the limb and spine, suggesting the appendicular and axial skeletons are subject to differential regulation by leptin. We established primary cultures for the chondrocytes from tibial and vertebral epiphyseal plates. Cellular proliferation and apoptosis were analyzed for the chondrocytes that had been treated with various concentrations of leptin. Crucial factors for chondrocyte proliferation and differentiation, such as BMP7 and Wnt3, were measured in the cells treated with leptin alone or in combination with pharmacological inhibitors of STAT and ERK signaling pathways. Primary culture of tibial epiphyseal plate chondrocytes has greater proliferating capability compared with that of vertebral epiphyseal plate chondrocytes. Leptin could promote the proliferation of tibial epiphyseal plate chondrocytes, while its effect on vertebral epiphyseal plate chondrocytes was inhibitory. Consistently, apoptosis is inhibited in tibial but promoted in vertebral epiphyseal plate chondrocytes by leptin. Importantly, leptin differentially modulates chondrogenic signaling pathways in tibial and vertebral epiphyseal chondrocytes through STAT and ERK pathways. Leptin differentially regulates chondrogenic proliferation and differentiation in appendicular and axial regions of the skeletons. The signaling pathways in these two regions are also distinct and subject to differential regulation by leptin through the STAT pathway in tibial epiphyseal plate chondrocytes but through the ERK pathway in vertebral epiphyseal plate chondrocytes. Therefore, the regulation of leptin is multi-faceted in the distinct anatomical regions of the skeleton. Knowledge gained from this system will provide insights into the pathophysiological causes for the diseases related to bone development and metabolism.

Targeting posttraumatic inflammation is crucial for improving locomotor function. SIRT1 has been shown to play a critical role in disease processes such as hepatic inflammation, rheumatoid arthritis, and acute lung inflammation by regulating inflammation. However, the role of SIRT1 in spinal cord injury (SCI) is unknown. We hypothesized that SIRT1 plays an important role in improving locomotor function after SCI by regulating neuroinflammation. In this study, we investigate the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes. First, we found that SIRT1 expression at the injured lesion site of wild-type (WT) mice (C57BL/6) decreased 4 h after SCI and lasted for 3 d. Moreover, administration of SRT1720, an agonist of SIRT1, to WT mice significantly improved functional recovery for up to 28 d after injury by reducing the levels of proinflammatory cytokines, the number of M1 macrophages, the number of macrophages/microglia, and the accumulation of perivascular macrophages. In contrast, administration of SRT1720 to SIRT1 knock-out (KO) mice did not improve locomotor recovery or attenuate inflammation. Furthermore, SIRT1 KO mice exhibited worse locomotor recovery, increased levels of inflammatory cytokines, and more M1 macrophages and perivascular macrophages than those of WT mice after SCI. Together, these findings indicate that SRT1720, an SIRT1 agonist, can improve functional recovery by attenuating inflammation after SCI. Therefore, SIRT1 is not only a protective factor but also an anti-inflammatory molecule that exerts beneficial effects on locomotor function after SCI.SIGNIFICANCE STATEMENTPosttraumatic inflammation plays a central role in regulating the pathogenesis of spinal cord injury (SCI). Here, new data show that administration of SRT1720, an SIRT1 agonist, to wild-type (WT) mice significantly improved outcomes after SCI, most likely by reducing the levels of inflammatory cytokines, the number of macrophages/microglia, perivascular macrophages, and M1 macrophages. In contrast, SIRT1 KO mice exhibited worse locomotor recovery than that of WT mice due to aggravated inflammation. Taken together, the results of this study expand upon the previous understanding of the functions and mechanisms of SIRT1 in neuroinflammation following injury to the CNS, suggesting that SIRT1 plays a critical role in regulating neuroinflammation following CNS injury and may be a novel therapeutic target for post-SCI intervention.

Objective: The lumbar ligamentum flavum (LF) is an important part of the spine to maintain the stability of the spine. In this study we aimed to examine whether mechanical force by cyclic stretch could induce apoptosis in human LF cells and investigate the underlying mechanism.Methods: LF cells were isolated from six young patients undergoing spinal surgery and then cultured in vitro. LF cells were subjected to cyclic stretch and the poptosis was detected by flow cytometry. The level of intracellular reactive oxygen species (ROS) and caspase-9 activity were measured.Results: Cyclic stretch at a frequency of 0.5 Hz with 20% elongation induced the apoptosis of human LF cells in vitro, and this was correlated with increased ROS generation and activation of caspase-9.Conclusion: Our study suggests that cyclic stretch-induced apoptosis in human LF cells may be mediated by ROS generation and the activation of caspase-9.

Background context Bulging of ligamentum flavum can happen with the aging process and can lead to compression of the spinal cord and nerves. However, the distribution and the risk factors associated with a missed ligamentum flavum bulge (LFB) are unknown. Purpose The aim was to evaluate the distribution and risk factors associated with missed LFB in the cervical spine. Study design This was a retrospective analysis of kinematic magnetic resonance images (kMRI). Patient sample Patients diagnosed with symptomatic neck pain or radiculopathy between March 2011 and October 2012 were included. Outcome measures The outcome measures were missed LFB and degenerative factors. Methods A total of 200 patients (1,000 cervical segments) underwent upright kMRI in neutral, flexion, and extension postures. The LFB, sagittal cervical angles, disc herniation, disc degeneration, disc height, angular motion, translational motion, age, and gender were recorded. After excluding segments with LFB in neutral and flexion position, Pearson and Spearman correlation coefficients were used to evaluate the relation between the risk factors and missed LFB in the extension position. Results The average depth of LFB was 0.24±0.71 mm at C2–C3, 1.02±1.42 mm at C3–C4, 1.65±1.48 mm at C4–C5, 2.13±1.37 mm at C5–C6, and 1.05±1.54 mm at C6–C7. The distribution of LFB was the most frequent at C5–C6 level (76.58%) followed by C4–C5 (63.06%). Disc herniation, disc degeneration, angular variation, and translational motion were significantly correlated with missed LFB at C4–C5 andC5–C6. Disc degeneration was the only factor significantly correlated with missed LFB at all cervical segments. Conclusions Occurrence and depth of missed LFB was the highest at C4–C5 and C5–C6 compared with other cervical levels. Disc degeneration, disc herniation, angular variation, and translational motion could play a role in the development of LFB at C4–C5 andC5–C6.

Objective To investigate the effect of asymmetric tension on idiopathic scoliosis (IS) and to understand its pathogenic mechanism. Methods The rodent model of scoliosis was established using Sprague–Dawley rats with left rib-tethering from T6 to T12, tail and shoulder amputation, and high-cage feeding. Vertebrae epiphyseal cartilage plates were harvested from the convex and concave sides. To analyze differences on the convex and concave sides, finite element analysis was carried out to determine the mechanical stress. Protein expression on epiphyseal cartilage was evaluated by western blot. Micro-CT was taken to evaluate the bone quality of vertebral on both sides. Results Scoliosis curves presented in X-ray radiographs of the rats. Finite element analysis was carried out on the axial and transverse tension of the spine. Stresses of the convex side were −170.14, −373.18, and −3832.32 MPa (X, Y, and Z axis, respectively), while the concave side showed stresses of 361.99, 605.55, and 3661.95 MPa. Collagen type II, collagen type X, Sox 9, RunX2, VEGF, and aggrecan were expressed significantly more on the convex side (P

A retrospective technical report.To assess the effect of bilateral C1 laminar hooks combined with C2 pedicle screw fixation for the treatment of C1-C2 instability.Various posterior atlantoaxial fixations for C1-C2 instability have been developed. However, due to anatomic anomalies of the vertebral artery, the smallness of the pedicle, trajectories of broken screws, or a lack of surgical experience, a simple atlantoaxial fixation technique with good safety and effectiveness is urgently needed.From January 2007 to September 2012, 18 patients with C1-C2 instability who underwent posterior bilateral C1 laminar hooks combined with C2 pedicle screw fixation were evaluated. Six patients had acute odontoid fractures (Anderson IIc type), 8 patients had odontoid pseudarthrosis, 3 had os odontoideum, and 1 had a traumatic rupture of the transverse ligament. The mean age at the time of surgery was 34.1 years. The clinical and radiographic analyses were performed before and after the operation and at follow-up.The follow-up period was 12-78 months (with an average follow-up period of 25.6 mo). All patients were relieved of pain and their neurological symptoms were substantially improved. The postoperative JOA score improved significantly (t=-7.234, P0.001). No neurological or vascular complications occurred in these cases. The device was placed well and had not loosened or broken and plain radiographs revealed bony fusion in 17 patients. One patient had C1 posterior arch fracture 3 weeks postoperatively and she was followed up for 18 months without revision surgery.When appropriate patients were selected, bilateral C1 laminar hooks combined with C2 pedicle screw fixation can be an alternative method to treat C1-C2 instability effectively with a relatively simple procedure. Preoperative planning and evaluation were crucial for the solid atlantoaxial fusion.

Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional differentiation potential, which can be used as seed cells to repair and reconstruct many types of tissues and organs following injury or disease. Osteogenic differentiation involves a variety of pathway and factors, including cytokines, growth factors, and hormones. In the present study, we investigated the potential role of Dishevelled in osteogenic differentiation of BMSCs in induction medium containing the methyltransferase inhibitor 5-aza-2’-deoxycytidine. The expression of Dishevelled was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) and a Western blot. The methylation degree of the CpG island in the promoter region of the Dishevelled gene was analyzed, and protein expression levels of Wnt, Glycogen synthase kinase-3 (GSK3), axin, Dishevelled, and β-catenin were increased after the addition of the methyltransferase inhibitor. The expression of Dishevelled increased in accordance with the differentiation of osteoblasts, and the degree of methylation of the promoter affected its expression level. In conclusion, regulating the methylation degree of the Dishevelled gene promoter region appears to influence the expression of Dishevelled and therefore the osteogenic differentiation of BMSCs.

Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor—p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.

Longitudinal bone growth is governed by a complex network of endocrine signals including leptin. In mouse, leptin deficiency leads to distinct phenotypes in bones of the limb and spine, suggesting the appendicular and axial skeletons are subject to differential regulation by leptin. We established primary cultures for the chondrocytes from tibial and vertebral epiphyseal plates. Cellular proliferation and apoptosis were analyzed for the chondrocytes that had been treated with various concentrations of leptin. Crucial factors for chondrocyte proliferation and differentiation, such as BMP7 and Wnt3, were measured in the cells treated with leptin alone or in combination with pharmacological inhibitors of STAT and ERK signaling pathways. Primary culture of tibial epiphyseal plate chondrocytes has greater proliferating capability compared with that of vertebral epiphyseal plate chondrocytes. Leptin could promote the proliferation of tibial epiphyseal plate chondrocytes, while its effect on vertebral epiphyseal plate chondrocytes was inhibitory. Consistently, apoptosis is inhibited in tibial but promoted in vertebral epiphyseal plate chondrocytes by leptin. Importantly, leptin differentially modulates chondrogenic signaling pathways in tibial and vertebral epiphyseal chondrocytes through STAT and ERK pathways. Leptin differentially regulates chondrogenic proliferation and differentiation in appendicular and axial regions of the skeletons. The signaling pathways in these two regions are also distinct and subject to differential regulation by leptin through the STAT pathway in tibial epiphyseal plate chondrocytes but through the ERK pathway in vertebral epiphyseal plate chondrocytes. Therefore, the regulation of leptin is multi-faceted in the distinct anatomical regions of the skeleton. Knowledge gained from this system will provide insights into the pathophysiological causes for the diseases related to bone development and metabolism.

Objective To evaluate the clinical use of kinetic magnetic resonance imaging (kMRI) in spinal degenerative diseases. Methods A systematic search of PubMed, EMBASE and ISI databases for articles that had been published between January 1978 and February 2013 concerning patients who had undergone kMRI for spinal problems was performed. All selected patients had undergone kMRI in neutral, flexion, and extension weight-bearing positions. Evaluation of cervical and lumbar degeneration by kMRI was analyzed. kMRI showed significant reduction of mobility in cervical segments of patients with severe disc degeneration; in addition, it was more severely reduced in patients with severe cord compression than in those without it. In the cervical spine, it was found that although disc height, translational motion, and angular variation were significantly affected at the level of disc herniation, no significant changes were apparent in adjacent segments. kMRI also showed that lumbar degeneration is closely associated with disc degeneration, facet joint osteoarthritis and the pathological characteristics of the interspinous ligaments, ligamentum flavum and paraspinal muscles. Results Eleven articles (4162 patients) fulfilled the inclusion criteria and were reviewed. It was found that kMRI is more specific and sensitive than conventional MRI regarding relating patients' symptoms to objective findings on imaging that demonstrate pathology and biomechanics. In the kinetic position, kMRI improves detection of disc herniation by 5.78%–19.46% and thus provides a new means of studying the biomechanical mechanism(s) in degenerative spines. Conclusion Kinetic MRI is effective for diagnosing, evaluating, and managing degenerative disease within the spine; however, it still has some limitations.

Objective To assess whether polymorphisms of the fat mass and obesity associated gene ( FTO) are associated with the presence and severity of degenerative disc disease (DDD) in a Chinese Han population. Methods In this case–control study, patients with DDD and controls matched for age, sex and body mass index were genotyped for six single nucleotide polymorphisms (SNPs) of FTO. Disease severity was measured using the Japanese Orthopaedic Association score. Allelic, genotypic and genotype–phenotype association analyses were performed. Results A total of 80 patients with DDD and 80 controls were studied. All six SNPs were in Hardy–Weinberg equilibrium. The frequencies of allele G and genotype G/G of the SNP rs11076008 were significantly associated with DDD after Bonferroni correction. No associations were shown between the SNPs studied and sex or disease severity. Conclusion The SNP rs11076008 of FTO may play an important role in the development of DDD in a Chinese Han population. The G/G genotype and/or G allele may be a risk factor for DDD. These results suggest that FTO is a DDD predisposition gene and may support a close relationship between obesity and DDD.

Background: Split spinal cord malformation (SSCM) is rare in scoliosis. This study evaluated the safety and effectiveness of one-stage surgical treatment of congenital scoliosis (CS) in patients with SSCM in a single Chinese center. Method: A retrospective study of 5 cases who underwent surgery for CS with SSCM (2 type I and 3 type II) from March 2004 to March 2012. Patients included 4 females and 1 male with a mean age of 13.8 years. All patients underwent one-stage posterior fusion surgery with resection of a bony spur firstly in SSCM type I, but we did nothing to the SSCM in type II. Clinical symptoms and radiological changes were evaluated preoperatively and for at least 2 years postoperatively. Results: Preoperatively, 5 patients had variant neurological and other symptoms. They had a mean preoperative Cobb angle of 63 ± 20° and T5-T12 kyphosis of 30 ± 21°. The mean postoperative Cobb angle was 30.2 ± 19.8° with a correction rate of 57.2 ± 17.0%. At the 3-month follow-up the Cobb angle loss was 3.0 ± 6.8°, and at the 2-year follow-up the Cobb angle loss was 6.5 ± 9.7°. Hyperkyphosis was significantly corrected after surgery but correction loss was indicated at the 2-year follow-up (p < 0.01). There were no neurological deficit complications or deteriorated neurological signs postoperatively or at follow-up. Conclusions: One-stage surgical treatment of CS with SSCM could be safe and effective, but we need further multicenter studies with larger samples. Intraspinal intervention of bone spur was recommended in SSCM type I before deformity correction, while in SSCM type II it was needless.

Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor—p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.

Several studies have shown that secreted phosphoprotein 24kD (Spp24) inhibits tumor growth. However, the effects of spp24 on hepatocellular carcinoma are not quite clear. In this study, we observed the inhibitory effect of spp24 on hepatocellular carcinoma in vivo. A subcutaneous hepatocellular carcinoma mice model was established by using Hep G2 cells. After sacrifice at day 40, tumor growth was assessed and tumor cell apoptosis and tumor cells proliferation were assessed by TUNEL assay and immunochemical analysis, respectively. BMP2 slightly stimulated the subcutaneous tumor growth compared with the control. Spp24 significantly inhibited the tumor growth and also abolished the BMP2-induced tumor growth (p

Study design Numerical techniques were used to study the vibration response of idiopathic scoliosis patients with single thoracic curve. Objective To analyze the dynamic characteristics of the idiopathic scoliotic spine under the whole-body vibration condition. The influence of the upper body mass was also studied. Summary of background data The relationship between the whole-body vibration and the spinal disorders has been investigated using finite element method. However, the dynamic response features of the scoliotic spine to the vibration were poorly understood. Methods The resonant frequencies of the scoliotic spine and the effects of the body weight were studied using a finite element model described previously. Modal and harmonic analysis was conducted. The amplitudes of 6 fundamental vertebral movements around the long, coronal and sagittal axis were quantified in the frequency range of 1 to 35 Hz. Results The vibration-induced rotation amplitudes of the apex of the thoracic deformity were higher than that of the lumbar segments. The apical vertebrae had the greatest rotation amplitudes at 2 and 8 Hz, and the largest lateral translation amplitudes at 16 Hz. Vibration could cause large lateral flexion amplitudes in the apex of the thoracic deformity. The apical vertebrae had the largest side flexion amplitudes at 6 Hz. Increasing upper body mass could not change resonant frequency of vibration-induced lateral translation and rotation around the long axis of the apical vertebrae. Conclusion The scoliotic spine is more sensitive to vibration than the normal spine. For a patient with single thoracic curve, long-term whole-body vibration may do more harm to the thoracic deformity than to the lower lumbar segments. Axial cyclic loads applied to an already deformed spine may cause further rotational and scoliotic deformity. The patients with idiopathic scoliosis are more likely to suffer from vibration-induced spinal disorders than those by normal persons.

Intraosseous ganglions are rare, benign lesion of bone that most frequently occur in the metaphyses of the long bones. These lesion are unusual in the scaphoid, most published reports are of individual cases1, 2. We here report a case of intraosseous ganglion of the scaphoid that was treated in our department.

The purpose of this study was to describe the clinical features of noncontiguous cervical degenerative disc disease (cDDD), investigate the efficacy and complications of a stand-alone anchored spacer (SAAS) for patients with noncontiguous cDDD, and present radiologic analysis of the intermediate segment (IS) after skip-level fusion. Nineteen consecutive patients with noncontiguous cDDD who underwent skip-level anterior cervical discectomy and fusion (ACDF) with SAAS from January 2010 to December 2012 were enrolled in this study. Clinical outcomes were assessed preoperatively and at 24 months postoperatively using the Japanese Orthopaedic Association score, Neck Disability Index, and Visual Analog Scale. Overall cervical alignment (OCA) of the cervical spine, and the range of motion (ROM), intervertebral disc height (IDH), disc signal intensity and disc protrusion of IS were measured and compared before and after surgery. Clinical outcomes significantly improved compared to preoperative scores. The OCA was corrected and maintained at 24 months postoperatively compared with preoperative values (p0.05). There were no significant differences in the ROM and IDH of the IS at each follow-up (p0.05). However, decreased signal intensity on T2-weighted MRI was evidenced in three mobile IS at final follow-up (20.0%). Skip-level ACDF with SAAS may be an efficacious option for the treatment of noncontiguous cDDD.

STUDY DESIGN Retrospective radiographical study. OBJECTIVE To define the relationship between the grade of disc degeneration and the motion of the lumbar spine by using kinetic magnetic resonance imaging. SUMMARY OF BACKGROUND DATA Disc degeneration is common after middle age. Lumbar instability has generally been recognized as a potential risk factor of low back pain. However, correlations between the grade of disc degeneration and the motion of the lumbar spine need more investigation. METHODS Kinetic magnetic resonance imaging was performed in 162 patients with symptomatic low back pain without prior history of surgery. The lumbar intervertebral discs were graded by spine surgeons according to the degenerative grading system (grades I-V). Translational motion and angular variation were measured at each segment from L1-L2 through L5-S1. The relationship between the degree of lumbar disc degeneration and extent of lumbar spine mobility was analyzed. RESULTS The translational motion in discs with grade I through IV increased gradually, but decreased with grade V. Compared with other less degenerative grades, grade V discs had significantly decreased total intervertebral translational motion (P < 0.05). The angular variation in discs with grade I through IV was fairly constant, but decreased with grade V. Compared with other degenerative grades (I-IV), grade V discs had significantly decreased total intervertebral translational motion (P < 0.05). For less degenerative grades I and II discs, the L2-L3 and L3-L4 segmental units contributed the majority of total angular mobility of the spine. However, for the severely degenerated segments, grade V discs, the contributions of the L2-L3 and L3-L4 significantly decreased (P < 0.01). CONCLUSION As disc degeneration developed from the normal to an increasingly severe stage, the motion of lumbar spine progressed from the normal stage to an unstable phase with higher mobility and finally to an ankylosed stage where stability was increased. LEVEL OF EVIDENCE 3.

Background Anterior cervical plate had developed continuously, and this study aimed to assess the biomechanics of a novel self-locking plate system for anterior cervical fixation designed by ourselves. Methods Twelve anterior cervical plates (i.e., six novel plates and six DePuy plates) were subjected to a pull-out test and a fatigue test. In addition, 12 C1-T1 cervical spine specimens underwent anterior cervical corpectomy and C5 fusion using six novel plates and six DePuy plates. Pre- and postoperative range of motion, load–displacement, axial stiffness, torque, and twisting stiffness were compared. Results No differences in maximum pull-out force, relative displacement, or energy absorption were observed between the DePuy plates and the novel plates (P >0.05). The novel plate system could bear an average of 5.6 × 105 times of loading, while the DePuy plate could bear 5.4 × 105 times of loading. The fatigue strengths of the new plate system and the DePuy plate were 490.75 and 485.86 MPa, respectively. No differences in fatigue life or strength were observed between the two types of plates. Cervical spine stability increased significantly after internal fixation. No differences in range of motion, load–displacement, axial stiffness, torque, or twisting stiffness were observed between the novel self-locking plate and the DePuy plate (P >0.05). Conclusions Compared to the DePuy plate, the novel anterior cervical self-locking plate system described here has good strength and fastening ability, allowing it to provide sufficient biomechanical stability. Further clinical assessment of this system is needed.

Although stand-alone cages were advocated to be superior to plate-cage construct (PCC) because of comparable clinical outcomes and fewer plate-related complications, cage dislocation and subsidence were frequently mentioned in multilevel fusion. There are some concerns about whether these issues can be effectively prevented in multilevel anterior cervical discectomy and fusion (ACDF) by stand-alone anchored spacer (SAAS).The aim was to compare clinical outcomes, radiologic parameters, and complications of PCC and SAAS in the treatment of three-level cervical spondylotic myelopathy (CSM).This was a retrospective comparative study.A total of 38 consecutive patients with three-level CSM (ACDF with PCC, 20 patients; ACDF with SAAS, 18 patients) were reviewed.Clinical outcomes were assessed using Japanese Orthopaedic Association and Neck Disability Index. The radiologic evaluations included cervical alignment (CA), segmental angle (SA), postoperative curvature loss (PCL), and incidence of subsidence.All the aforementioned parameters were compared before and after surgery between two groups. Besides, the aforementioned results were also compared between the two groups. The complications were also recorded.The mean follow-up period was 30.3 months. No significant differences were observed in clinical outcomes between the two groups (p.05). Additionally, no significant differences existed in fusion rate between the two groups. There were significant differences in PCL of SA and CA and correction of SA between the two groups (p.05). Besides, the incidence of subsidence (9 of 54 levels, 16.7%) was recorded in the SAAS group, and the potential of SAAS to reduce the incidence of postoperative dysphagia was not proven. No other complications were observed in this study.In the surgical treatment of three-level CSM, PCC is superior to SAAS in correction and maintenance of SA and avoiding cage subsidence, although the technique of ACDF with SAAS yielded encouraging clinical outcomes and high fusion rate.

STUDY DESIGN A kinematic magnetic resonance imaging study. OBJECTIVE To investigate the distribution of Schmorl nodes (SNs) in the lumbar spine in healthy adults, and determine the association with lumbar disk degeneration and lumbar spine motion. SUMMARY OF BACKGROUND DATA SNs have been associated with several pathologies of the lumbar spine, although it has been demonstrated that they also occur in the healthy adult population without a clearly identified cause. A thorough understanding of SN distribution may help reveal reasons for their formation. How disk degeneration and lumbar spine motion relate to SNs is poorly understood. METHODS Kinematic magnetic resonance images (0.6 T) were available for 1179 healthy individuals from 15 to 85 years of age. Spine specialists performed computer-based measurements. All parameters were measured and calculated automatically using the eRAD PACS Viewer (eRAD Inc., version 6.2.1.1). Lumbar disk degeneration was documented according to the Pfirrmann classification system. Lumbar spine lordosis was quantified as the angle between the inferior endplate of L1 and superior endplate of S1. The level of significance was defined as P ≤ 0.05. The distribution of SNs along the lumbar spine and their relationship with age and sex was investigated using the single factor analysis of variance χ test. The relationship between SNs, age group, disk location, and overall grades of lumbar disk degeneration were investigated by multiple logistic regression analysis. Lumbar spine motion was compared between patients with and without SNs via independent t test among 585 individuals with qualified kinematic images. Multiple logistic regression analysis was performed on associations of lumbar motion range among the SN population. RESULTS The prevalence of SNs in our study population was 28.4%, and SNs were observed to be present more frequently in males (34.6%) than in females (20.2%) (ρ< 0.01). There was no significant difference in the incidence of SNs between age groups (ρ= 0.18). SNs were more common at the L2 and L3 vertebral bodies (14.3% and 14.4%), whereas SNs were least common at S1 vertebral bodies (1.5%). The highest incidences of SNs presentation was on disks with degeneration grade III (41.9%) and grade IV (45.3%). SN occurrence, aging, and disk location were positively correlated with lumbar disk degeneration grade. The lumbar spine range of motion was significantly different between individuals with and without SNs (31.4° vs. 37.9°, ρ< 0.01). The frequency of SNs was associated with decreased lumbar range of motion in all age groups except 51 to 60 years and 61 to 70 years. CONCLUSION SNs have a high incidence in individuals without persistent lumbar disorders and were found in disks at all degrees of degeneration. SNs occurrence were positively associated with lumbar disk degeneration In addition, the presence of SNs was correlated with decreased overall lumbar motion across all age groups.

Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. Recent data indicate that miR-155 plays a crucial role in the pathogenesis of different fibrotic diseases. This study aimed to test the hypothesis that miR-155 exerts effects on LF thickness by regulating collagen expression. We found that LF thickness and the expression of collagen I and, collagen III were higher in LF from LSS patients than in LF from lumbar disc herniation (LDH) patients (P<0.01). The expression of miR-155 was significantly higher in LF from LSS group than in LF from LDH group (P<0.01). miR-155 level was positively correlated with LF thickness (r=0.958,P<0.01), type I collagen level (r=0.825,P<0.01), and type III collagen level (r=0.827,P<0.01). miR-155 mimic increased mRNA and protein expression of collagen I and collagen III in fibroblasts isolated from LF, while miR-155 sponge decreased mRNA and protein expression of collagen I and III in fibroblasts. In conclusions, miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy.

Background context The treatment of adolescent congenital deformity (late-diagnosed congenital deformity) is still unknown. The best candidates for hemivertebra excision are young patients, typically between 4 and 6 years of age. Partial excision may be feasible for older children. Purpose The purpose of this study was to assess the effect of unilateral pedicle subtraction osteotomy of hemivertebra for correction of the adolescent congenital spinal deformity. Study design Retrospective analysis. Patient sample Twelve patients with adolescent congenital deformity who underwent posterior unilateral pedicle subtraction osteotomy and correction were evaluated. Mean age at the time of surgery was 17 years. Outcome measures The charts, standing full-length posteroanterior and lateral view radiographs, and functional measures were reviewed. Methods For evaluation of surgical effectiveness, comparative analysis of the parameters of the total main curve, the segmental curve, the compensatory cranial and caudal curves, the segmental kyphosis, and the trunk shift before and after operation and at the most recent follow-up was done. Results The mean follow-up period was 40.5 months. Mean Cobb angles of the total main curve and the segmental curve were, respectively, 47.5° and 43.8° before surgery, 23.7° and 16.5° after surgery, and 22.6° and 17° at the last follow-up. The angle of segmental kyphosis was 11.8° before surgery, 6.2° after surgery, and 7.8° (range, −30° to 26°) at the final follow-up. The mean final global lordosis was within the normal range. No neurologic deficit occurred. Solid fusion was achieved for all cases. Conclusions Unilateral pedicle subtraction osteotomy with instrumentation from a posterior-only approach is indicated in older teenagers for an adolescent congenital spinal deformity. Compared with hemivertebra excision, corrective surgery with hemivertebra osteotomy has a lower intraoperative blood loss and shorter operation time.

To establish the artificial bladder reflex arc by the normal body reflex pathway above the horizon of spinal cord injury to reinnervate the flaccid bladder and restore bladder micturition function.An intradural microanastomosis was performed on the L6 ventral root to the S2 ventral root. After axonal regeneration,the "patellar ligament-spinal cord center-bladder" reflex pathway was reestablished. A long-term function of the reflex arc was observed in the nerve electrophysiological experiment, detrusor electromyography experiment, and urodynamic testing 8 months after anastomosis.Trains of the stimuli (200 microV, 5 ms) in the left L6 dorsal root and the nerve at the anastomosized site resulted in motor evoked potential from the distal to the anastomosized site before and after the spinal cord was destroyed horizontally between S1 and S4 segment levels in 2 Beagle dogs. The figure and amplitude of the evoked potential were similar to those of the control and general stability which showed a noninterventional wave. The urodynamic test revealed a rapid increase of the bladder pressure and a minor increase in the abdominal pressure. This showed that the bladder detrusor mainly resulted in the pressure increase. The bladder pressure increased to 60% of the normal on average compared with the controls when resulted in the left L6 dorsal root and the nerve anastomosized site were stimulated.The long-term observation by the nerve electrophysiological experiment, detrusor electromyography experiment, and urodynamic test indicate that the new artificial reflex arc can be established successfully. The somatic motor axons can regenerate into the parasympathetic endoneurial tubes of the autonomic nerve.

To study the advance in the treatment of atonic bladder after spinal cord injury.The recent literature concerned was extensively reviewed and some methods of therapy for atonic bladder were introduced.No effective method of therapy was found for atonic bladder after spinal cord injury. When compared with clean intermittent catheterization, pharmacologic therapy, compressive micturition and detrusor function reconstruction, the establishment of an artificial bladder reflex arc may have a potential of controllable micturition.To establish an artificial bladder reflex may provide an update of current therapeutic concepts for atonic bladder after spinal cord injury.

Background There is considerable controversy as to which posterior technique is best for the treatment of multi-level cervical spondylotic myelopathy. The aim of this study was to compare the clinical and radiographic results and complications of laminoplasty (LAMP) and laminectomy (LAMT) in the treatment of multi-level cervical spondylotic myelopathy. Methods We reviewed and analyzed papers published from January 1966 and June 2013 regarding the comparison of LAMP and LAMT for multi-level cervical spondylotic myelopathy. Statistical comparisons were made when appropriate. Results Fifteen studies were included in this systematic review. There was no significant difference in the incidence of surgical complications between LAMP and LAMT. Compared to conventional LAMT and skip LAMT, postoperative ROM was more limited in LAMP, but this was still superior to postoperative ROM following LAMT with fusion. Postoperative kyphosis occurred in 8/180 (4.44%) in LAMP and 13/205 (6.34%) in LAMT, whereas no cases of kyphosis were reported for skip LAMT. Skip LAMT appears to have better clinical outcomes than LAMP, while the outcome was similar between LAMP and LAMT with fusion. Conclusions Based on these results, a claim of superiority for laminoplasty or laminectomy was not justified. In deciding between the two procedures, the risks of surgical and neurological complications, and radiologic and clinical outcome, must be taken into consideration if both options are available in multi-level cervical spondylotic myelopathy.