High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis

Wu, Yuantao; Zhang, Hongqi; Tang, Mingxing; Guo, Chaofeng; Deng, Ang; Li, Jiong; Wang, Yunjia; Xiao, Lairong; Yang, Guanteng

doi:10.1186/s12967-020-02367-z

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…[22] Epigenetics, including DNA methylation, is an important environmental factor that plays a vital role in CS development. [23] We found reduced FGF23 gene DNA methylation levels in CS patients compared with their identical twins by targeted-region methylation sequencing, and CS patients had increased mRNA levels of FGF23, consistent with the clinical symptoms of their low BMD.…”

Section: Discussionsupporting

confidence: 62%

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway

Zhang

Xiang

et al. 2023

Chinese Medical Journal

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Background: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. Methods: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. Results: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. Conclusions: Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.

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Section: Discussionsupporting

confidence: 62%

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway

Zhang

Xiang

et al. 2023

Chinese Medical Journal

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“…In addition to BRD1, we obtained several other Hub genes that are closely related to immunological aspects of OA. KAT6B gene, located in the 10q22.2 region [38], is a member of the MYST family of histone acetyltransferases. It can acetylate the lysine 23 residue of histone H3 (H3K23ac) [39].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based analysis of potential candidates chromatin regulators for immune infiltration in osteoarthritis

Wang¹,

Ou²,

Peng

et al. 2022

BMC Musculoskelet Disord

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Background Through the bioinformatics analysis to screen out the potential chromatin regulators (CRs) under the immune infiltration of osteoarthritis (OA), thus providing some theoretical support for future studies of epigenetic mechanisms under OA immune infiltration. Methods By integrating CRs and the OA gene expression matrix, we performed weighted gene co-expression network analysis (WGCNA), differential analysis, and further screened Hub genes by protein-protein interaction (PPI) analysis. Using the OA gene expression matrix, immune infiltration extraction and quantification were performed to analyze the correlations and differences between immune infiltrating cells and their functions. By virtue of these Hub genes, Hub gene association analysis was completed and their upstream miRNAs were predicted by the FunRich software. Moreover, a risk model was established to analyze the risk probability of associated CRs in OA, and the confidence of the results was validated by the validation dataset. Results This research acquired a total of 32 overlapping genes, and 10 Hub genes were further identified. The strongest positive correlation between dendritic cells and mast cells and the strongest negative correlation between parainflammation and Type I IFN reponse. In the OA group DCs, iDCs, macrophages, MCs, APC co-inhibition, and CCR were significantly increased, whereas B cells, NK cells, Th2 cells, TIL, and T cell co-stimulation were significantly decreased. The risk model results revealed that BRD1 might be an independent risk factor for OA, and the validation dataset results are consistent with it. 60 upstream miRNAs of OA-related CRs were predicted by the FunRich software. Conclusion This study identified certain potential CRs and miRNAs that could regulate OA immunity, thus providing certain theoretical supports for future epigenetic mechanism studies on the immune infiltration of OA.

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“…In general, genetic variants and epigenetic modifications are pivotal causes to embryonic somatogenesis failure. 2,26 Environmental factors, including hypoxia, are validated principal regulators of fibroblast growth factor (FGF) signaling, which is an essential pathway in the pathogenesis of CS. 2 Up until now, the epigenetic modification of CS is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis

Liu

Zhao

Yan

et al. 2021

Molecular Therapy - Nucleic Acids

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Congenital scoliosis (CS) is a congenital disease caused by malformations of vertebrae. Recent studies demonstrated that DNA modification could contribute to the pathogenesis of disease. This study aims to identify epigenetic perturbations that may contribute to the pathogenesis of CS. Four CS patients with hemivertebra were enrolled and underwent spine correction operations. DNA was extracted from the hemivertebrae and spinal process collected from the specimen during the hemivertebra resection. Genome-wide DNA methylation profiling was examined at base-pair resolution using whole-genome bisulfite sequencing (WGBS). We identified 343 genes with hyper-differentially methylated regions (DMRs) and 222 genes with hypo-DMRs, respectively. These genes were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, calcium signaling pathway, and axon guidance in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and were enriched in positive regulation of cell morphogenesis involved in differentiation, regulation of cell morphogenesis involved in differentiation, and regulation of neuron projection development in Biological Process of Gene Ontology (GO-BP) terms. Hyper-DMR-related genes, including IGHG1, IGHM, IGHG3, RNF213, and GSE1, and hypo DMR-related genes, including SORCS2, COL5A1, GRID1, RGS3, and ROBO2, may contribute to the pathogenesis of hemivertebra. The aberrant DNA methylation may be associated with the formation of hemivertebra and congenital scoliosis.

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High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis

Cited by 13 publications

References 31 publications

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway

Bioinformatics-based analysis of potential candidates chromatin regulators for immune infiltration in osteoarthritis

Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis

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