Learning curve of junior surgeons in robot-assisted pedicle screw placement: a comparative cohort study.

OBJECTIVE: Robot-assisted technology has been gradually applied to pedicle screw placement in spinal surgery. This study was designed to detailedly evaluate the learning curve of junior surgeons in robot-assisted spine surgery. METHODS: From December 2020 to February 2022, 199 patients requiring surgical treatment with posterior pedicle screw fixation were prospectively recruited into the study. The patients were randomized to the robot-assisted group (the RA group) or the conventional freehand group (the CF group). Under the senior specialist's supervision, pedicle screws were placed by two junior fellows without prior experience. Cumulative summation (CUSUM) analysis was performed on the learning curve of pedicle screw placement for performing quantitative assessment based on the time of screw insertion. RESULTS: In total, 769 and 788 pedicle screws were placed in the RA and CF groups. Compared with the CF group, the learning duration in the RA group was shorter in the upper thoracic region (57 vs. 70 screws), but longer in the lower thoracic (62 vs. 58 screws) and the lumbosacral region (56 vs. 48 screws). The slope of learning curve was lower in the RA group than in the CF group. The screw accuracy in the RA group was superior to that in the CF group, especially in upper thoracic region (89.4% vs. 76.7%, P < 0.001). This disparity of accuracy became wider in deformity cases. In the upper thoracic region, the mean placement time was 5.34 ± 1.96 min in the RA group and 5.52 ± 2.43 min in the CF groups, while in the lower thoracic and lumbosacral regions, the CF group's mean placement times were statistically shorter. Three screw-related neural complications occurred in the CF group. CONCLUSION: Robot-assisted technique has its advantages in the upper thoracic region and deformity cases, which is easier and safer to insert pedicle screws. The robot-assisted technique allowed a short learning curve for junior surgeons and exhibited consistently excellent results even in the early application period.

C-type lectin domain-containing protein CLEC3A regulates proliferation, regeneration and maintenance of nucleus pulposus cells.

It is widely assumed that as connective tissue, the intervertebral disc (IVD) plays a crucial role in providing flexibility for the spinal column. The disc is comprised of three distinct tissues: the nucleus pulposus (NP), ligamentous annulus fibrous (AF) that surrounds the NP, and the hyaline cartilaginous endplates (CEP). Nucleus pulposus, composed of chondrocyte-like NP cells and its secreted gelatinous matrix, is critical for disc health and function. The NP matrix underwent dehydration accompanied by increasing fibrosis with age. The degeneration of matrix is almost impossible to repair, with the consequence of matrix stiffness and senescence of NP cells and intervertebral disc, suggesting the value of glycoproteins in extracellular matrix (ECM). Here, via database excavation and biological function screening, we investigated a C-type lectin protein, CLEC3A, which could support differentiation of chondrocytes as well as maintenance of NP cells and was essential to intervertebral disc homeostasis. Furthermore, mechanistic analysis revealed that CLEC3A could stimulate PI3K-AKT pathway to accelerate cell proliferation to further play part in NP cell regeneration.

Antinociceptive effect of intrathecal injection of miR-9-5p modified mouse bone marrow mesenchymal stem cells on a mouse model of bone cancer pain.

BACKGROUND: A growing body of studies have indicated that bone marrow mesenchymal stem cells (BMSCs) have powerful analgesic effects in animal models of bone cancer pain. Here, we explored the molecular mechanisms underlying how BMSCs alleviate pain sensation in a mouse model of bone cancer pain. METHODS: C3H/HeN adult male mice were used to generate a bone cancer pain model. BMSCs were isolated from mouse bone marrow, modified by transfection with microRNA-9-5p (miR-9-5p), and infused into the spinal cord. Spontaneous flinches, paw withdrawal latency, limb-use score, and weight-bearing score were used to assess pain-related behaviors. ELISA, RT-PCR, western blot, and luciferase assay were used to assess gene expressions. RESULTS: Our results show that miR-9-5p regulated the expression of both repressor element silencing transcription factor (REST) and µ-opioid receptors (MOR) by targeting REST in primary mouse BMSCs. Overexpression of miR-9-5p reversed the activation of inflammatory pathway in TNF-α- and IL-6-treated BMSCs. In addition, miR-9-5p modified BMSCs alleviated cancer pain in the sarcoma-inoculated mouse model. MiR-9-5p modified BMSCs suppressed cytokine expression in the spinal cord of sarcoma-inoculated mice by suppressing REST gene expression. CONCLUSIONS: Our results indicate that miR-9-5p modified BMSCs can relieve bone cancer pain via modulating neuroinflammation in the central nervous system, suggesting genetically modified BMSCs could be a promising cell therapy in pain management.

Selective thoracolumbar/lumbar fusion for Syringomyelia-associated scoliosis: a case-control study with Lenke 5C adolescent idiopathic scoliosis.

BACKGROUND: Selective thoracolumbar/lumbar fusion technique was introduced to treat adolescent idiopathic scoliosis (AIS) patients with major thoracolumbar/lumbar curves. Theoretically, this surgical strategy could also be applied to syringomyelia patients. No previous study has specifically addressed the effectiveness of selective thoracolumbar/lumbar fusion for patients with syringomyelia-associated scoliosis. The aim of the study was to investigate the effectiveness of selective thoracolumbar/lumbar fusion for the surgical treatment of patients with syringomyelia-associated scoliosis. METHODS: From February 2010 to September 2016, 14 syringomyelia-associated patients with major thoracolumbar/lumbar curves were retrospectively reviewed. Besides, 30 Lenke 5C AIS patients were enrolled as a control group. Posterior selective thoracolumbar/lumbar fusion was performed for both groups. Patients' demographic, operative, radiological, and quality of life data were reviewed with follow-up. Intragroup comparisons were performed for each parameter. RESULTS: The two groups were matched by age, gender, curve characteristics, duration of follow-up, and all preoperative radiographic parameters except for thoracic kyphosis. After surgery, the average correction rate of the major thoracolumbar/lumbar curve was 82.2 ± 7.8% in the syringomyelia group, which was not significantly different from that of AIS group (82.5 ± 10.6%, P = 0.47). A similar improvement of unfused thoracic curve was observed between the two groups (50.1 ± 16.5% vs. 48.5 ± 26.9%, P = 0.29). During the follow-up, the correction effect of scoliosis was well maintained, without aggravation of the original neural symptoms or fresh permanent neurological deficits. Of note, the number of fusion levels was significantly larger in syringomyelia group than that in AIS group (7.6 ± 1.4 vs. 6.5 ± 1.2, P < 0.01). The average follow up was 47.6 months (36-81 months). CONCLUSION: Similar to AIS cases, syringomyelia-associated scoliosis can be effectively and safely corrected by selective thoracolumbar/lumbar fusion with satisfactory surgical outcomes. However, the syringomyelia group, on average, required an additional fused segment for treatment as compared to the AIS group (7.6 versus 6.5 in the AIS group).

An Agonist of the Protective Factor SIRT1 Improves Functional Recovery and Promotes Neuronal Survival by Attenuating Inflammation after Spinal Cord Injury.

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 STATEMENT Posttraumatic 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.

Leptin differentially regulates endochondral ossification in tibial and vertebral epiphyseal plates.

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.

Leptin differentially regulates chondrogenesis in mouse vertebral and tibial growth plates.

BACKGROUND: Leptin plays an important role in mediating chondrogenesis of limb growth plate. Previous studies suggest that bone structures and development of spine and limb are different. The expression of Ob-Rb, the gene that encodes leptin receptors, is vertebral and appendicular region-specific, suggesting the regulation of leptin on VGP and TGP chondrogenesis may be very different. The aim of the present study was to investigate the differential regulation of leptin on the chondrogenesis of vertebral growth plate (VGP) and tibial growth plate (TGP). METHODS: We compared the VGP and TGP from wild type (C57BL/6) and leptin-deficient (ob/ob) mice. We then generated primary cultures of TGP and VGP chondrocytes. By treating the primary cells with different concentrations of leptin in vitro, we analyzed proliferation and apoptosis of the primary chondrocytes from TGP and VGP. We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin. RESULTS: Leptin-deficient mice of 8-week-old had shorter tibial and longer vertebral lengths than the wide type mice. Disturbed columnar structure was observed for TGP but not for VGP. In primary chondrocyte cultures, leptin inhibited VGP chondrocyte proliferation but promoted their apoptosis. Collagen IIA and aggrecan mRNA, and the protein levels of proliferation- and chondrogenesis-related markers, including PCNA, Sox9, and Smad4, were downregulated by leptin in a dose-dependent manner. In contrast, leptin stimulated the proliferation and chondrogenic differentiation of TGP chondrocytes at physiological levels (i.e., 10 and 50 ng/mL) but not at high levels (i.e., 100 and 1000 ng/mL). CONCLUSION: Leptin exerts a stimulatory effect on the proliferation and chondrogenic differentiation of the long bone growth plate but an inhibitory effect on the spine growth plate. The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and metabolism.

Fibroblast growth factor-21 concentration in serum and synovial fluid is associated with radiographic bone loss of knee osteoarthritis.

We aimed to evaluate whether FGF-21 concentration in serum and synovial fluid (SF) is associated with radiographic bone loss of knee osteoarthritis (OA). A total of 186 OA patients and 108 controls were recruited. The radiographic bone loss of knee OA was assessed by the Ahlbäck grading scale. FGF-21 concentration in serum and SF was measured by enzyme-linked immunosorbent assay (ELISA). We demonstrated that OA patients had significantly higher serum FGF-21 concentration compared with controls (204.30 [range 158.25-279.16] ng/L vs. 130.72 [range 94.93-218.03] ng/L, p < 0.01). FGF-21 concentration in serum was well correlated with that in paired SF samples (r = 0.668, p < 0.001). In OA patients, those with a higher Ahlbäck grade had significantly higher serum and SF FGF-21 concentration (p < 0.001 for both). FGF-21 concentration in serum and SF was significantly and independently associated with the Ahlbäck grade (r = 0.403, p < 0.001 and r = 0.410, p < 0.001; respectively). These findings indicated that FGF-21 might be a potential biomarker for predicting bone loss of OA. Therapeutic interventions by blocking FGF-21 signaling pathways to delay the degenerative process of OA warrants further investigations.

Split spinal cord malformation: report of 5 cases in a single Chinese center and review of the literature.

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.

Is Complete Correction of Cervical Sagittal Malalignment Necessary During 4-Level Anterior Cervical Discectomy and Fusion Surgery in Patients With Kyphosis?

STUDY DESIGN: Retrospective analysis. OBJECTIVE: We investigated whether complete correction of cervical sagittal malalignment is necessary during 4-level anterior cervical discectomy and fusion (ACDF) in patients with kyphosis. METHODS: This retrospective study included 84 patients who underwent 4-level ACDF surgery at a university hospital between January 2010 and December 2015. Based on the degree of cervical lordosis correction, patients were categorized into the following groups: mild (0-10°), moderate (10-20°), and complete correction (>20°). The clinical outcomes, radiological parameters, and functional outcomes were analyzed. RESULTS: We observed no significant intergroup differences in the baseline characteristics. The cervical sagittal vertical axis (CSVA) correction loss at the final follow-up was lesser in the mild- and moderate- than in the complete-correction group. The spinocranial angle (SCA) and T1 slope (T1 S) were significantly higher in the moderate- and complete-correction groups than in the mild-correction group, 3 days postoperatively. The cervical proximal junctional kyphosis (CPJK), adjacent segment degeneration (ASD), and ASD following CPJK rates were higher in the complete-correction group. We observed no significant intergroup differences in postoperative complications; however, 5 patients showed internal fixation failure in the complete-correction group; 4 of these patients required reoperation. No significant intergroup difference was observed in the Japanese Orthopedic Association and neck disability index scores at any time point. CONCLUSIONS: A mild-to-moderate correction of cervical lordosis is superior to complete correction in patients with kyphosis who undergo 4-level ACDF because this approach is associated with lesser axial stress and CSVA correction loss.

Leptin accelerates BMSC transformation into vertebral epiphyseal plate chondrocytes by activating SENP1-mediated deSUMOylation of SIRT3.

Bone marrow mesenchymal stem cells (BMSCs) are capable of multidirectional differentiation, and engrafted BMSCs can be used to replace damaged chondrocytes for treatment of intervertebral disc disease. However, chondroblast differentiation of implanted BMSCs is inhibited by the anoxic environment of the articular cavity. Here, we found that leptin enhanced the transformation of BMSCs into chondrocytes under hypoxic conditions. BMSCs isolated from mice were cultured in medium supplemented with leptin under hypoxia. The expression of MFN1/2 and OPA1 were increased only in BMSCs cultured in an anoxic environment. In addition, in hypoxic environments cell energy metabolism relies on glycolysis regulated by leptin, rather than by mitochondrial oxidation. The expression of the de-SUMOylation protease SENP1 was elevated, leading to SIRT3-mediated activation of PGC-1α; these processes were regulated by CREB phosphorylation, and promoted mitochondrial fusion and cell differentiation. The chondrogenic activity of BMSCs isolated from SIRT3-knockout mice was lower than that of BMSCs isolated from wildtype mice. Implantation of SIRT3-knockout murine-derived BMSCs did not significantly improve the articular cartilage layer of the disc. In conclusion, the hypoxic microenvironment promoted BMSC differentiation into chondrocytes, whereas osteoblast differentiation was inhibited. SENP1 activated SIRT3 through the deSUMOylation of mitochondria and eliminated the antagonistic effect of SIRT3 acetylation on phosphorylation. When phosphorylation activity of CREB was increased, phosphorylated CREB is then transferred to the nucleus, affecting PGC-1α. This promotes mitochondrial fusion and differentiation of BMSCs. Leptin not only maintains chondrogenic differentiation homeostasis of BMSCs, but also provides energy for differentiation of BMSCs under hypoxic conditions through glycolysis.

Impacts of age and gender on bone marrow profiles of BMP7, BMPRs and Stro-1⁺ cells in patients with total hip replacement.

PURPOSE: A successful osseointegration relies on the interplay of implant surface and surrounding bone marrow cells. This study was undertaken to investigate the impact of age and gender on the bone marrow composition. METHODS: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 24 patients with total hip replacement. Flow cytometry was used to measure the expression of Stro-1(+) cells and BMP receptors (BMPRs)-expressing cells. ELISA was used to measure bone marrow aspirate bone morphology protein7 (BMP7) concentration. RESULTS: Our data demonstrates that there are diverse bone marrow profiles (Stro-1(+) cell and BMPRs(+) cells). There are no differences of Stro-1(+) cells, BMPRs(+) cells, and BMP7 concentration between male and female patients. Though there are slight increases in the number of Stro-1(+) cells and BMPRs(+) cells in younger patients (<70 years old) than those of old patients (≥ 70 years old), the difference is not statistically significant. However, we found a close association between the Stro-1(+) cells, BMPR1a cells and BMP7 concentration. In addition, a correlation exists between the number of Stro-1(+) cells and BMIs of these patients. CONCLUSION: Our data suggests that the age and gender of THR patients have little impact on their bone marrow osteogenic potential. The significance of the number of the Stro-1(+) with BMPRs expression on the implant fixation and osseointegration warrants further investigation.

Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis.

PURPOSE: This study measured high-mobility group box 1 (HMGB-1) levels in serum and synovial fluid (SF) in patients with primary knee osteoarthritis (OA) and correlated these levels with radiographic disease severity. METHODS: Seventy-eight OA patients and 30 controls were enrolled in this study. All OA patients were scored according to the Kellgren-Lawrence (KL) grading system. HMGB-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: SF HMGB-1 levels were significantly higher in knee OA patients, compared with controls (P < 0.01). Moreover, SF HMGB-1 levels were positively associated with KL scores (P < 0.01). Multinomial logistic regression demonstrated that the SF HMGB-1 level was an independent factor for radiographic severity of OA (P=0.002); however, serum HMGB-1 levels did not differ significantly between OA patients and controls and did not correlate with KL scores (P > 0.05). CONCLUSION: These results demonstrate that HMGB-1 levels in SF of knee OA patients are independently associated with radiographic disease severity.

MiR-874-3p plays a protective role in intervertebral disc degeneration by suppressing MMP2 and MMP3.

Intervertebral disc degeneration (IDD) is a spinal degenerative disease and one of the most important causes of musculoskeletal disability. Matrix metalloproteinase (MMP)-mediated extracellular matrix degradation is the core process of IDD. The regulators of MMPs in the intervertebral disc are still not fully known. In this study, using quantitative reverse transcription PCR, luciferase reporter assay, Western blotting, immunofluorescence, flow cytometry, and Cell Counting Kit-8 assay, we found that the miR-874-3p expression level was significantly decreased in IDD patients. MiR-874-3p could target and repress MMP2 and MMP3 expression in nucleus pulposus cells. These results could improve the understanding of IDD and provide a possible diagnostic marker and treatment candidate for IDD. The miR-874-3p/MMP2/MMP3 axis might also provide direction for future cancer and inflammation investigations.

Circular RNA Expression Profile in Patients with Lumbar Spinal Stenosis Associated with Hypertrophied Ligamentum Flavum.

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.

Inclination of the small laminar slope angle leads to lumbar spinal stenosis due to hypertrophy of the ligamentum flavum.

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.

SIRT6 enhances telomerase activity to protect against DNA damage and senescence in hypertrophic ligamentum flavum cells from lumbar spinal stenosis patients.

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 ß-galactosidase (SA-ß-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.

[The effect of the thoracic cage on the vertebral axial rotation of adolescent idiopathic scoliosis: a biomechanical study].

OBJECTIVE: To investigate the effect of the rib cage on the vertebral axial rotation of adolescent idiopathic scoliosis under axial load condition. METHODS: Three dimensional finite element model of adolescent idiopathic scoliosis included and excluded thoracic cage was built based on the data of computer tomography. The model was imported into the preprocessor of the ANSYS 8.0 software for assigning boundary and loading conditions. Then the axial loading condition was simulated after entering the solution modular. The magnitude and direction of each vertebral axial rotation of the scoliotic spine were read and analyzed in the postprocessor of the ANSYS software. RESULTS: The rib cage had a significant influence on the axial rotation of the vertebra above the structural curve and had no influence on the axial rotation of the lumbar and sacral vertebra. The effect of the thoracic cage on the axial rotation of the apical vertebra was limited. Under different loading conditions, the apical vertebra of both models rotated in the same direction. The magnitude of the vertebral rotation of both models has no statistical significance. CONCLUSIONS: Adolescent idiopathic scoliosis can lead to the anatomical changes of the vertebra and the thoracic cage. The corresponding changes of biomechanical features of the scoliotic spine and rib cage would occur. The deformed thoracic cage could not maintain the rotation stability as the normal one.

Polydatin induces apoptosis and autophagy via STAT3 signaling in human osteosarcoma MG-63 cells.

Polydatin, a natural product, is detected in many daily diets, such as grape juices and peanut. Autophagy regulation is recognized as a new potential strategy for cancer therapy, and previous studies demonstrated that polydatin showed remarkable anti-cancer ability. Nevertheless, the capability of polydatin to induce autophagy and its role in anti-osteosarcoma remains obscure. In this study, we investigated the anticancer effect of polydatin on human osteosarcoma cell line MG-63 and its underlying mechanism. Our results indicated that polydatin significantly inhibited proliferation of MG-63 cells in a dose- and time-dependent manner, and increased their apoptosis and autophagic flux. Further experiments showed that polydatin reduced the expression and phosphorylation (Y705) level of STAT3 (Signal transducer and activator of transcription 3), increased the expression of autophagy-related genes (Atg12, Atg14, BECN1, PIC3K3), and therewith triggered autophagic cell death in MG-63 cells. Of note, the cytotoxicity effect of polydatin was rescued by co-treatment with Colivelin (STAT3 activator), suggesting the dependency of MG-63 cells on STAT3 for survival in this process. Moreover, polydatin-triggered autophagy and apoptosis were remarkably reduced following exposure to autophagy inhibitor 3-methyladenine, while cell viability was increased. In conclusion, these data demonstrated that polydatin induced MG-63 cell death through inducing apoptosis, and autophagy which was mediated via the STAT3 signaling. Therefore, polydatin might be a potential clinical drug in the remedy of osteosarcoma.

[Combined pedicle subtraction osteotomy and polysegmental closing wedge osteotomy for correction of the severe thoracolumbar kyphotic deformity in ankylosing spondylitis].

OBJECTIVE: To study retrospectively the efficacy and complications of combined pedicle subtraction osteotomy (PSO) and polysegmental closing wedge osteotomy for correction of the severe rigid thoracolumbar kyphotic deformity in ankylosing spondylitis (AS). METHODS: A total of 8 consecutive male patients with AS and severe thoracolumbar kyphotic deformity (mean age 32 years, range 28 - 46) were involved in this study from August 2004 to June 2007. The average preoperative Cobb angle of thoracic spine (T(1)-T(12)) was 96 degrees (range, 80 degrees - 112 degrees ), the mean preoperative angle of lumbar lordosis (L(1)-S(1)) was 10 degrees (5 degrees - 15 degrees ). The mean chin-brow angle was 47 degrees (range, 40 degrees - 58 degrees ). The average gaze angle was 43 degrees (range, 32 degrees - 50 degrees ). After preoperative assessment, single-level PSO was performed in L(3) vertebrae and two-level polysegmental closing wedge osteotomy was performed in thoracolumbar vertebrae (T(12)-L(1), L(1-2)). Radiographic and clinical results and complications were assessed. RESULTS: The surgical time was (298.1 +/- 20.7) minutes and blood loss during the procedure was (1588.8 +/- 171.6) ml. The follow-up period was (11.5 +/- 7.7) months. The postoperative angle and the amount of correction of the thoracic and lumbar spine were 76.1 degrees +/- 9.6 degrees , 20.3 degrees +/- 1.1 degrees and 48.4 degrees +/- 4.7 degrees , 38.4 degrees +/- 4.7 degrees respectively. The postoperative chin-brow and gaze angle was 16.5 degrees +/- 4.6 degrees and 73.0 degrees +/- 5.2 degrees , respectively. The amount of correction for sagittal balance was (12.3 +/- 1.6) cm. No nerve, vascular injury, stress fracture and coronal decompensation occurred in the patients. CONCLUSIONS: Combined PSO and polysegmental closing wedge osteotomy by posterior approach only is safe and effective for correction of the severe rigid thoracolumbar kyphotic deformity in AS. The visual field is significantly improved after surgery.