Abstract
BackgroundIdiopathic 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.ResultsCompared 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.ConclusionsThus, 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.
Highlights
Idiopathic scoliosis (IS) is a complex disease with an unclear etiology, and the worldwide prevalence is approximately 2–3%
We examined the mRNA levels of extracted primary chondrocyte extracellular matrix components aggrecan (ACAN), collagen type II (COL2A1), and collagen type X (COL10A1), which is a reliable marker for new bone formation in articular cartilage [21, 22]
Alteration in histone methylation in the facet joint chondrocytes of IS patients compared with the control group Given that histone methylation plays important roles in chondrocyte proliferation and hypertrophy [23], we detected
Summary
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. 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. In addition to growth-related factors, joint hypermobility may be susceptible to spinal instability and the development of IS, since researchers have found that girls with IS have significantly more laxity than that of healthy sex- and age-matched controls [6, 7]. Li et al Clinical Epigenetics (2019) 11:107 abnormal growth of the vertebral column may be tightly associated with the development of IS
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