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  • 1
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    Online Resource
    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)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    URL: Article
    DOI: 10.1186/s12967-020-02367-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2118570-0
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  • 2
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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)
    Type of Medium: Online Resource
    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
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2737824-X
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  • 3
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    Dysregulation of the ghrelin/RANKL/OPG pathway in bone mass is related to AIS osteopenia
    Elsevier BV ; 2020
    In:  Bone Vol. 134 ( 2020-05), p. 115291-
    Details
    In: Bone, Elsevier BV, Vol. 134 ( 2020-05), p. 115291-
    Type of Medium: Online Resource
    ISSN: 8756-3282
    URL: Article
    DOI: 10.1016/j.bone.2020.115291
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1496324-3
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  • 4
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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
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1466-1861 , 0962-9351
    URL: Article
    DOI: 10.1155/2021/5537811
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2008065-7
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  • 5
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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
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2020/4243015
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2698540-8
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  • 6
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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)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1471-2474
    URL: Article
    DOI: 10.1186/s12891-022-05730-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041355-5
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  • 7
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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
    Abstract: 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
    Type of Medium: Online Resource
    ISSN: 0362-2436 , 1528-1159
    URL: Article
    DOI: 10.1097/BRS.0000000000003849
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 8
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    Phosphorylated heat shock protein 27 improves the bone formation ability of osteoblasts and bone marrow stem cells from patients with adolescent idiopathic scoliosis
    Wiley ; 2023
    In:  JOR SPINE Vol. 6, No. 3 ( 2023-09)
    Details
    In: JOR SPINE, Wiley, Vol. 6, No. 3 ( 2023-09)
    Abstract: Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real‐time PCR (qRT–PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.
    Type of Medium: Online Resource
    ISSN: 2572-1143 , 2572-1143
    URL: Issue
    URL: Article
    DOI: 10.1002/jsp2.v6.3
    DOI: 10.1002/jsp2.1256
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2931784-8
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  • 9
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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
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    URL: Article
    DOI: 10.1097/CM9.0000000000002165
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 10
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    Table_2.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Surgery Vol. 9 ( 2022-4-4)
    Details
    In: Frontiers in Surgery, Frontiers Media SA, Vol. 9 ( 2022-4-4)
    Abstract: Autogenous bone grafts, such as iliac bone or rib struts, have been used in the anterior reconstruction of spinal tuberculosis (STB) and have their own benefits and limitations. Here, we introduced a new method, the spinous process (SP), combined with a titanium mesh cage (TMC) as a bone graft in the stability reconstruction of lumbar or lumbosacral STBs. By retrospectively comparing patients who received SP+TMC to traditional TMC bone grafts or allogeneic bone grafts in terms of safety, efficacy and cost-effectiveness, we aimed to evaluate whether SP+TMC could be a possible alternative method. Methods From 2010 to 2018, 69 patients who underwent one-stage posterior debridement with grafts and internal fixation within a single lumbar or lumbosacral segment were included in this study. Twelve patients who received SP combined with a TMC (SP+TMC, group A), 30 patients who received a TMC only (group B), and 27 patients who received allografts (group C) were included. Measurements including operative time, blood loss, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association Impairment (ASIA) grade, final follow-up (FFU) duration and postoperative complications were recorded. Radiological measurements, including the number of segments fixated, the number of pedicle screws used, the Cobb angle, pelvic parameters, and the bony fusion time, were reviewed. All outcomes were analyzed using SPSS 25. Results We found that the SP+TMC group had fewer fixation segments, fewer pedicle screws implanted, a shorter operative time, reduced blood loss, and a considerably lower hospital cost than allografts. In addition, the TMC group had a comparable clinical outcome with the TMC group regarding lower economic cost. Conclusion Our study demonstrates that compared to a TMC or allograft, the use of SP combined with a TMC as a bone graft is an effective and reliable approach for the surgical management of one-level lumbar or lumbosacral spinal tuberculosis, leading to effective restoration of spinal stability. Furthermore, this approach is a cost-effective structural bone grafting method, especially for patients in developing countries.
    Type of Medium: Online Resource
    ISSN: 2296-875X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fsurg.2022.818926
    DOI: 10.3389/fsurg.2022.818926.s001
    DOI: 10.3389/fsurg.2022.818926.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2773823-1
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