CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis.

Background: Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin-1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs). Methods: The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation-regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co-expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS. Results: Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation. Conclusions: Taken together, our systems-level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

Incidence of Subsidence of Seven Intervertebral Devices in Anterior Cervical Discectomy and Fusion: A Network Meta-Analysis.

BACKGROUND: Subsidence is an incapacitating complication in anterior cervical discectomy and fusion (ACDF). However, the debate over which of the intervertebral devices is associated with lower incidence of subsidence remains to be settled. METHODS: Seven dominant techniques comprising cage with plate (CP), iliac bone graft with plate (IP), Zero-profile cage with screws (Zero-P), ROI-C cages with clips (ROI-C), polyether ether ketone cage alone (PCA), iliac crest autogenous graft (ICAG), and titanium cage alone (TCA) were examined. The incidences of subsidence in the different groups were calculated and compared. RESULTS: A total of 30 studies with 2264 patients were identified. Overall, the CP group presented the lowest incidence of subsidence, and its incidence was significantly lower than that in the Zero-P group, the PCA group, the ICAG group, and the TCA group (P < 0.05). The incidence of subsidence in the IP group was significantly lower than that in the PCA group, the ICAG group, and the TCA group (P < 0.05). In single-level ACDF, the CP group presented the lowest incidence of subsidence, and its incidence was significantly lower than that in the PCA group and the TCA group (P < 0.05). No difference was found between single-level and multilevel ACDF and the incidence of subsidence was higher in those undergoing single-level ACDF. CONCLUSIONS: CP and IP resulted in a lower rate of subsidence than cage alone or ICAG. Zero-P and ROI-C cages led to similar subsidence rates with plate. All types of intervertebral device can be applied to both single-level and multilevel ACDF with comparable subsidence rate.

Long-term Results Comparing Cervical Disc Arthroplasty to Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Whether cervical disc arthroplasty (CDA) is superior to anterior cervical discectomy and fusion (ACDF) remains controversial, especially in relation to long-term results. The present study aimed to evaluate the long-term safety and efficiency of CDA and ACDF for cervical disc disease. METHODS: We performed this study according to the Cochrane methodology. An extensive search was undertaken in PubMed, Embase, and Cochrane databases up to 1 June 2019 using the following key words: "anterior cervical fusion," "arthroplasty," "replacement" and "artificial disc". RevMan 5.3 (Cochrane, London, UK) was used to analyze data. Safety and efficiency outcome measures included the success rate, functional outcome measures, adverse events (AE), adjacent segment degeneration (ASD), secondary surgery, and patients' satisfaction and recommendation rates. The OR and MD with 95% confidence interval (CI) were used to evaluate discontinuous and continuous variables, respectively. The statistically significant level was set at P < 0.05. RESULTS: A total of 11 randomized controlled trials with 3505 patients (CDA/ACDF: 1913/1592) were included in this meta-analysis. Compared with ACDF, CDA achieved significantly higher overall success (2.10, 95% CI [1.70, 2.59]), neck disability index (NDI) success (1.73, 95% CI [1.37, 2.18]), neurological success (1.65, 95% CI [1.24, 2.20]), patients' satisfaction (2.14, 95% CI [1.50, 3.05]), and patients' recommendation rates (3.23, 95% CI [1.79, 5.80]). Functional outcome measures such as visual analog score neck pain (-5.50, 95% CI [-8.49, -2.52]) and arm pain (-3.78, 95% CI [-7.04, -0.53]), the Short Form-36 physical component score (SF-36 PCS) (1.93, 95% CI [0.53, 3.32]), and the Short Form-36 mental component score (SF-36 MCS) (2.62, 95% CI [0.95, 4.29]), revealed superiority in the CDA group. CDA also achieved a significantly lower rate of symptomatic ASD (0.46, 95% CI [0.34, 0.63]), total secondary surgery (0.50, 95% CI [0.29, 0.87]), secondary surgery at the index level (0.46, 95% CI [0.29, 0.74]), and secondary surgery at the adjacent level (0.37, 95% CI [0.28, 0.49]). However, no significant difference was found in radiological success (1.35, 95% CI [0.88, 2.08]), NDI score (-2.88, 95% CI [-5.93, 0.17]), total reported AE (1.14, 95% CI [0.92, 1.42]), serious AE (0.89, 95% CI [0.71, 1.11]), device/surgery-related AE (0.90, 95% CI [0.68, 1.18]), radiological superior ASD (0.63, 95% CI [0.28, 1.43]), inferior ASD (0.45, 95% CI [0.19, 1.11]), and work status (1.33, 95% CI [0.78, 2.25]). Furthermore, subgroup analysis showed different results between US and non-US groups. CONCLUSION: Our study provided further evidence that compared to ACDF, CDA had a higher long-term clinical success rate and better functional outcome measurements, and resulted in less symptomatic ASD and fewer secondary surgeries. However, worldwide multicenter RCT with long-term follow up are still needed for further evaluation in the future.

Complications of Full-Endoscopic Versus Microendoscopic Foraminotomy for Cervical Radiculopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Minimally invasive surgery of posterior cervical foraminotomy (PCF) for symptomatic radiculopathy has gained popularity in the last decade. It remains to be determined whether the 2 dominant operation techniques, full-endoscopic (FE) or microendoscopic (MI), are associated with fewer complications. METHODS: An electronic retrieval from PubMed, Embase, and Web of Science was performed to identify comparative or single-arm studies concerning FE-PCF and MI-PCF. The pooled incidence of complications was calculated. RESULTS: A total of 26 studies with 2028 patients (FE, 402; MI, 1626) were identified. The overall complication rate was 5.8% for FE-PCF and 3.5% for MI-PCF, with no significant difference (P = 0.115). The pooled complication rate for single-level radiculopathy showed no statistical difference (FE, 4.5%; MI, 3.5%; P = 0.471), either. However, constituent of complications showed apparent disparity, with transient root palsy in FE-PCF (15/19, 78.9%) and dural tear (20/47, 42.6%) in MI-PCF being the most commonly reported. As for the subgroup analysis, both incidence of dural tear (FE, 1.5%; MI, 1.8%; P = 0.672) and superficial wound infection (FE, 2.2%; MI, 1.0%; P = 0.109) showed no statistical difference. Nevertheless, transient root palsy occurred at a higher incidence in the FE group than in the MI group (FE, 4.5%; MI, 1.5%; P = 0.002). CONCLUSIONS: Both FE-PCF and MI-PCF can offer relatively safe treatment for cervical radiculopathy. There is no significant difference in overall complication rate between the 2 techniques. Dural tear is the most commonly reported complication of MI-PCF, whereas transient root palsy deserves to be noticed for surgeons performing FE-PCF.