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  • 1
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    Dysregulated Bone Metabolism Is Related to High Expression of miR-151a-3p in Severe Adolescent Idiopathic Scoliosis
    Hindawi Limited ; 2020
    In:  BioMed Research International Vol. 2020 ( 2020-09-27), p. 1-12
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2020 ( 2020-09-27), p. 1-12
    Kurzfassung: Adolescent idiopathic scoliosis (AIS) is a common complex disease, and bone homeostasis plays an important role in its pathogenesis. Recent advances in epigenetic research show that dysregulated miRNAs may participate in the development of orthopedic diseases and AIS. The aim of this study was to detect differentially expressed miRNAs in severe AIS and elucidate the mechanism of miRNA deregulation in the pathogenesis of AIS. In the present study, miRNA expression profiles were detected in severe and mild AIS patients as well as healthy controls by miRNA sequencing. Candidate miRNAs were validated in a larger cohort. Primary osteoblasts from severe AIS patients were extracted and isolated to determine the effect of the candidate miRNAs on bone metabolism. Finally, we determined the methylation level in primary osteoblasts from severe AIS patients. The result showed that miR-151a-3p was overexpressed in severe AIS patients. Reduced GREM1 expression was observed in primary osteoblasts from severe AIS patients. miR-151a-3p directly inhibited GREM1 in primary osteoblasts. Relatively lower methylation levels were detected in primary osteoblasts from severe AIS patients. In conclusion, our study revealed that plasma miR-151a-3p levels may serve as a biomarker for severe AIS. Overexpression of miR-151a-3p may interrupt bone homeostasis via inhibiting GREM1 expression. Our result may provide a new biomarker for the early detection of AIS and increase our understanding of the pathogenesis of AIS.
    Materialart: Online-Ressource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2020/4243015
    Sprache: Englisch
    Verlag: Hindawi Limited
    Publikationsdatum: 2020
    ZDB Id: 2698540-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Abnormal TNS3 gene methylation in patients with congenital scoliosis
    Springer Science and Business Media LLC ; 2022
    In:  BMC Musculoskeletal Disorders Vol. 23, No. 1 ( 2022-08-20)
    Details
    In: BMC Musculoskeletal Disorders, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-08-20)
    Kurzfassung: Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. Methods Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. Results A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected ( TNS3 , SEMAC3 , GPR124 , MEST , DLK1 , SNTG1 , PPIB , DEF8 , and GRHL2 ). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group ( p  = 0.00070  〈  0.01). There was no significant difference in the degree of methylation of SEMAC3 , GPR124 , MEST , DLK1 , SNTG1 , PPIB , DEF8 , or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P  = 0.003  〈  0.01). Conclusion Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.
    Materialart: Online-Ressource
    ISSN: 1471-2474
    URL: Article
    DOI: 10.1186/s12891-022-05730-x
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2022
    ZDB Id: 2041355-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Altered Circulating Cell-free Mitochondrial DNA of Patients with Congenital Scoliosis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Spine Vol. 46, No. 8 ( 2021-04-15), p. 499-506
    Details
    In: Spine, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 8 ( 2021-04-15), p. 499-506
    Kurzfassung: Case–control study. Objective. The aim of this study was to estimate the relationship between circulating cell-free DNA (ccf DNA) and clinical parameters of patients with congenital scoliosis (CS). Summary of Background Data. CS is a complex spinal deformity characteristic of congenital vertebral malformations. Although numerous studies have centered on the etiology of CS, the cause of CS remains unclear. Previously, we reported that circulating cell-free DNA (ccf DNA) is altered in adolescent idiopathic scoliosis ( AIS). However, the relationship between ccf DNA and the clinical parameters of patients with CS remains unclear. Methods. The plasma of peripheral blood from 35 patients with CS and 32 age-matched controls was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between ccf n-DNA and ccf mt-DNA levels were conducted. Receiver-operating characteristic (ROC) curves were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. Results. The plasma ccf mt-DNA levels of both ND1 and CYTC were significantly decreased in patients with CS compared with levels in controls both in total and by sex, whereas the plasma ccf n-DNA levels showed no significant difference. There is no difference in both ccf mt-DNA and ccf n-DNA between S-SDV and M-SDV according to The International Consortium for Vertebral Anomalies and Scoliosis (ICVAS) classification. The ROC curve analyses showed a reliable sensitivity and specificity of CS predicted by ccf mt-DNA levels in total but failed to distinguish different ICVAS types. Conclusion. Significantly decreased plasma ccf mt-DNA levels were observed in patients with CS compared with those in controls. Although this finding has limited significance for clinical practice, it indicates that ccf mt-DNA may predict the onset or development of CS. Further studies should focus on the role of ccf mt-DNA in embryo development and whether ccf mt-DNAs could be considered as a marker for prenatal screening in development disorder like CS. Level of Evidence: 4
    Materialart: Online-Ressource
    ISSN: 0362-2436 , 1528-1159
    URL: Article
    DOI: 10.1097/BRS.0000000000003849
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 2002195-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Halo traction combined with posterior-only approach correction for cervical kyphosis with Neurofibromatosis-1: minimum 2 years follow-up
    Springer Science and Business Media LLC ; 2021
    In:  BMC Musculoskeletal Disorders Vol. 22, No. 1 ( 2021-12)
    Details
    In: BMC Musculoskeletal Disorders, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Kurzfassung: Surgical management of cervical kyphosis in patients with NF-1 is a challenging task. Presently, anterior-only (AO), posterior-only (PO) and combined anterior-posterior (AP) spinal fusion are common surgical strategies. However, the choice of surgical strategy and application of Halo traction remain controversial. Few studies have shown and recommended posterior-only approach for cervical kyphosis correction in patients with NF-1. The aim of this study is to evaluate the safety and the effectiveness of halo Traction combined with posterior-only approach correction for treatment of cervical kyphosis with NF-1. Methods Twenty-six patients with severe cervical kyphosis due to NF-1 were reviewed retrospectively between January 2010 and April 2018. All the cases underwent halo traction combined with posterior instrumentation and fusion surgery. Correction result, neurologic status and complications were analyzed. Results In this study, cervical kyphosis Cobb angle decreased from initial 61.3 ± 19.7 degrees to postoperative 10.6 ± 3.7 degrees (P 〈 0.01), with total correction rate of 82.7%, which consist of 45.8% from halo traction and 36.9% from surgical correction. JOA scores were improved from preoperative 13.3 ± 1.6 to postoperative 16.2 ± 0.7 (P 〈 0.01). Neurological status was also improved. There was no correction loss and the neurological status was stable in mean 43 months follow-up. Three patients experienced minor complications and one patient underwent a second surgery. Conclusion Halo traction combined with PO approach surgery is safe and effective method for cervical kyphosis correction in patients with NF-1. A satisfied correction result, and successful bone fusion can be achieved via this procedure, even improvement of neurological deficits can also be obtained. Our study suggested that halo traction combined with PO approach surgery is another consideration for cervical kyphosis correction in patients with NF-1.
    Materialart: Online-Ressource
    ISSN: 1471-2474
    URL: Article
    DOI: 10.1186/s12891-021-04864-8
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2041355-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis
    Springer Science and Business Media LLC ; 2020
    In:  Journal of Translational Medicine Vol. 18, No. 1 ( 2020-12)
    Details
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Kurzfassung: The etiology of congenital scoliosis (CS) is complex and uncertain. Abnormal DNA methylation affects the growth and development of spinal development. In this study, we investigated the role of DNA methylation in CS. Methods The target region DNA methylation level in the peripheral blood of patients with CS was analyzed. Through in-depth analysis, genes closely related to the growth and development of the vertebra were identified. EdU staining was performed to verify the role of differentially expressed genes in chondrocyte proliferation. Results The hypermethylated KAT6B gene was observed in patients with CS, and was positively correlated with the Cobb angle. KAT6B was primarily expressed on chondrocytes. The promoter of KAT6B in CS patients was hypermethylated, and its expression was significantly reduced. Further mechanistic studies revealed that EZH2 mediated trimethylation of lysine 27 on histone H3 of the KAT6B promoter. Overexpression of KAT6B in CS-derived primary chondrocytes can significantly promote chondrocyte proliferation, which may be related to activation of the RUNX2/Wnt/β-catenin signaling pathway. Conclusion Epigenetic modification of KAT6B may be a cause of CS. If similar epigenetic modification abnormalities can be detected through maternal liquid biopsy screening, they may provide useful biomarkers for early screening and diagnosis of CS.
    Materialart: Online-Ressource
    ISSN: 1479-5876
    URL: Article
    DOI: 10.1186/s12967-020-02367-z
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2020
    ZDB Id: 2118570-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Data_Sheet_2.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-11-4)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2020-11-4)
    Materialart: Online-Ressource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2020.582255
    DOI: 10.3389/fcell.2020.582255.s001
    DOI: 10.3389/fcell.2020.582255.s002
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2020
    ZDB Id: 2737824-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Nontargeted Metabolomic Analysis of Plasma Metabolite Changes in Patients with Adolescent Idiopathic Scoliosis
    Hindawi Limited ; 2021
    In:  Mediators of Inflammation Vol. 2021 ( 2021-5-25), p. 1-11
    Details
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2021 ( 2021-5-25), p. 1-11
    Kurzfassung: Objective. Adolescent idiopathic scoliosis (AIS) is a relatively common spinal rotation deformity, and the pathogenesis of AIS is accompanied by metabolic dysfunction and changes in biochemical factors. In this study, plasma metabolite changes in AIS patients were analyzed based on nontargeted metabolomics to provide new insights for clarifying functional metabolic abnormalities in AIS patients. Methods. Clinical indexes and blood samples were collected from 12 healthy subjects and 16 AIS patients. Metabolomics was used to analyze the changes in metabolites in plasma samples. The correlation between plasma metabolites and clinical indexes was analyzed by the Spearman rank correlation coefficient. Results. Analysis of clinical data showed that the body weight, body mass index (BMI), and bone mineral density (BMD) index of the AIS group significantly decreased, while the blood phosphorus and Cobb angles increased significantly. Metabolomic analysis showed significant changes in 72 differential metabolites in the plasma of the AIS group, mainly including organooxygen compounds, carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, and keto acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that arginine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle (TCA cycle) were significantly enriched in the AIS and healthy groups. Spearman rank correlation coefficient analysis showed that the plasma metabolites C00026 (oxoglutarate), C00062 (L-arginine, arginine), C01042 (N-acetylaspartate), and C00158 (citrate) were significantly correlated with clinical indexes in AIS patients. In the healthy group, the plasma metabolites C00122 (fumarate), C00025 (glutamate and L-glutamic acid) and C00149 (malate, L-malic acid) were significantly correlated with clinical indexes, while C00624 (N-acetylglutamate) was not significantly correlated with the clinical indexes. Conclusion. The occurrence of AIS led to changes in clinical indexes and plasma metabolites. Plasma biomarkers and functional metabolic pathways were correlated with clinical indexes, which might provide new insights for the diagnosis and treatment of AIS.
    Materialart: Online-Ressource
    ISSN: 1466-1861 , 0962-9351
    URL: Article
    DOI: 10.1155/2021/5537811
    Sprache: Englisch
    Verlag: Hindawi Limited
    Publikationsdatum: 2021
    ZDB Id: 2008065-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Chinese Medical Journal Vol. 136, No. 17 ( 2022-12-24), p. 2077-2085
    Details
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 17 ( 2022-12-24), p. 2077-2085
    Kurzfassung: Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear. Methods: A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis. Results: A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17 , DCLK1 , PCDH7 , TSPAN5 , NHSL2 , and CPT1B . Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group. Conclusion: Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
    Materialart: Online-Ressource
    ISSN: 0366-6999 , 2542-5641
    URL: Article
    DOI: 10.1097/CM9.0000000000002165
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 2108782-9
    SSG: 6,25
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Preoperative Halo-Femoral Traction With Posterior Surgical Correction for the Treatment of Extremely Severe Rigid Congenital Scoliosis (Cobb Angle 〉120°)
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Academy of Orthopaedic Surgeons Vol. 30, No. 9 ( 2022-05-1), p. 421-427
    Details
    In: Journal of the American Academy of Orthopaedic Surgeons, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 9 ( 2022-05-1), p. 421-427
    Kurzfassung: To evaluate the effectiveness and safety of preoperative halo-femoral traction (HFT) with posterior surgical correction for the treatment of extremely severe rigid congenital scoliosis ( 〉 120°). Methods: We reviewed the records of all patients with extremely severe rigid congenital scoliosis ( 〉 120°) treated with preoperative HFT from 2010 through 2018. Radiographic measurements were performed. The period of traction, blood loss, operation time, complications, and pulmonary function test results were recorded. Results: A total of 11 patients were included in the study. All patients underwent preoperative HFT with posterior surgical correction. The mean preoperative main curve Cobb angle was 127.9° ± 4.4°, and the average correction rate was 33.5% posttraction, 54.8% postoperation, and 55.3% at the latest follow-up. Pulmonary function improved significantly after traction, and forced vital capacity and forced expiratory volume in 1 second increased from 34.7% and 33.4% to 48.1% and 48.5%, respectively. Only one patient experienced halo pin infection during HFT. No patients experienced permanent neurologic deficits or death. Conclusion: For extremely severe rigid congenital scoliosis with a Cobb angle greater than 120°, preoperative HFT with posterior surgical correction offers an effective and safe corrective option. The perioperative complication rate can be partially reduced. Study Design: Retrospective study.
    Materialart: Online-Ressource
    ISSN: 1067-151X , 1940-5480
    URL: Article
    DOI: 10.5435/JAAOS-D-21-01095
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    Standort Signatur Einschränkungen Verfügbarkeit
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