Suv39h1 promotes facet joint chondrocyte proliferation by targeting miR-15a/Bcl2 in idiopathic scoliosis patients

Abstract

Background Idiopathic scoliosis (IS) is a complex disease with an unclear etiology, and the worldwide prevalence is approximately 2–3%. As an important link between environmental factors and phenotypic differences, epigenetic changes, such as lncRNA, miRNA, and DNA methylation, have recently been reported to be associated with the development of IS. However, the correlation between histone methylation, another classical epigenetic mechanism, and IS has not been determined. In this study, we investigated the morphological changes, alterations in the levels of histone methylation, and cell proliferation-related pathway in inferior facet joint cartilage in 11 IS patients and 10 comparable controls. Results Compared with the control group, narrowed facet joint cartilage but increased proliferative chondrocytes and upregulated collagen type II ( COL2A1 ) and B-cell lymphoma-2 (Bcl2) were observed in IS patients. Additionally, tri-methylation levels of H3K9 (H3K9me3) rather than other lysine sites were significantly increased in IS patients, coinciding with the upregulation of its specific enzyme, suppressor of variegation 3-9, drosophila homolog of 1 (SUV39H1). In addition, Bcl2-targeted miR-15a was downregulated in IS patients, and the level of H3K9me3 in the promoter region of the miR-15a host gene was remarkably increased in IS patients compared with the control group. Moreover, overexpressing SUV39H1 in ATDC5 cells with increased H3K9me3 levels led to similar changes, with increased expression of COL2A1 and Bcl2, decreased expression of miR-15a, and increased cell proliferation. Conclusions Thus, our study suggests that increased chondrocyte proliferation occurs in the facet joint cartilage of IS patients compared with the control group and may be promoted by the elevated levels of H3K9me3 and SUV39H1, which regulate the miR-15a/Bcl2 pathway. This dysregulation of chondrocyte proliferation could result in abnormal spinal growth and may additionally participate in the development and progression of IS. Electronic supplementary material The online version of this article (10.1186/s13148-019-0706-1) contains supplementary material, which is available to authorized users.

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

“…In the research of congenital diseases, abnormal DNA methylation patterns can cause imprinting dysfunction, which will affect the growth and development of the fetus, leading to the occurrence of genetic diseases, such as Beckwith-Weidemann syndrome (BWS) and Prader-Willi/Angelman syndrome [12][13][14]. Researchers believe that DNA methylation plays an important role in the differentiation of specific tissues and organs, such as the vertebral column [15].…”

Single‐Cell Integration Analysis of Heterotopic Ossification and Fibrocartilage Developmental Lineage: Endoplasmic Reticulum Stress Effector Xbp1 Transcriptionally Regulates the Notch Signaling Pathway to Mediate Fibrocartilage Differentiation

“…Some information also implied the developmental potential of HO2 cells to become HO1 cells. For example, (1) Sox9, Col1a1, and Col2a1 have been shown to play important functions in cartilage development [ 89 , 90 ]; (2) Mgp was found to be related to the onset of osteoarthritis during cartilage development [ 91 ]; (3) Bcl2 was a key protein of the PI3K-AKT signaling pathway, which was closely associated with chondrocyte proliferation [ 92 ]; and (4) COL5A1 polymorphism was associated with susceptibility to tendon disease [ 93 ]. Notably, Gli3 , Cli2 , Pecam1 , and Ptch2 were found to be the star genes of the Hh signaling pathway, and Notch2 and Jag1 are the star genes of the Notch signaling pathway, suggesting that the activity of the Notch and Hh signaling pathways may be upregulated in HO1 cells [ 94 – 97 ].…”

Changes in circulating cell-free nuclear DNA and mitochondrial DNA of patients with adolescent idiopathic scoliosis

“…The qPCR was performed as previous with specific primers for the nucleic genes and mitochondrial genes respectively (Table 2) [21, 22]. The concentration of ccf n-DNA in plasma were expressed as genome equivalent/ml according to the qPCR results of Glyceraldehyde 3-phosphate dehydrogenase ( GAPDH ) and beta-actin ( ACTB ).…”