Dataset Information

Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis.

ABSTRACT: Adolescent idiopathic scoliosis (AIS) is a complex, three dimensional deformity of the spine that commonly occurs in pubescent girls. Abnormal osteogenic differentiation of mesenchymal stem cells (MSCs) is implicated in the pathogenesis of AIS. However, the biological roles of long noncoding RNAs (lncRNAs) in the regulation of osteogenic differentiation of MSCs are unknown. Through microarray analyses of bone marrow (BM) MSCs from healthy donors and AIS patients, we identified 1483 differentially expressed lncRNAs in AIS BM-MSCs. We defined a novel lncAIS (gene symbol: ENST00000453347) is dramatically downregulated in AIS BM-MSCs. In normal BM-MSCs, lncAIS interacts with NF90 to promote HOXD8 mRNA stability that enhances RUNX2 transcription in BM-MSCs, leading to osteogenic differentiation of normal BM-MSCs. By contrast, lncAIS downregualtion in AIS BM-MSCs cannot recruit NF90 and abrogates HOXD8 mRNA stability, which impedes RUNX2 transcription for osteogenic differentiation. Thereby lncAIS downregualtion in BM-MSCs suppresses osteogenic differentiation that is implicated in the pathogenesis of AIS.

SUBMITTER: Zhuang Q

PROVIDER: S-EPMC6748078 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis.

Zhuang Qianyu Q Ye Buqing B Hui Shangyi S Du Ying Y Zhao Robert Chunhua RC Li Jing J Wu Zhihong Z Li Na N Zhang Yanbin Y Li Hongling H Wang Shengru S Yang Yang Y Li Shugang S Zhao Hong H Fan Zusen Z Qiu Guixing G Zhang Jianguo J

Cell death and differentiation 20181121 9

Adolescent idiopathic scoliosis (AIS) is a complex, three dimensional deformity of the spine that commonly occurs in pubescent girls. Abnormal osteogenic differentiation of mesenchymal stem cells (MSCs) is implicated in the pathogenesis of AIS. However, the biological roles of long noncoding RNAs (lncRNAs) in the regulation of osteogenic differentiation of MSCs are unknown. Through microarray analyses of bone marrow (BM) MSCs from healthy donors and AIS patients, we identified 1483 differentiall ...[more]

PMID: 30464226

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Project description:Adolescent Idiopathic Scoliosis (AIS) is the most common orthopedic condition requiring surgery, affecting 4% of adolescents. There is currently no proven method or prognostic test to identify symptomatic patients at risk of developing severe scoliosis who could benefit from growth-guided devices or minimally invasive non-fusion instrumentation surgeries. These innovative treatments must be performed at an early disease stage in younger patients to benefit from their growth potential. In this prospective cross-sectional study, we investigated the clinical utility of circulating microRNAs (miRNAs), an important class of small non-coding RNA, as biomarkers to predict the risk of developing severe scoliosis in AIS. Blood samples and clinical data were collected from 116 AIS patients who were followed until skeletal maturity and stratified according to their clinical outcome. Genome-wide expression profiling of miRNAs was performed with plasma obtained at the time of diagnosis of AIS (mean age of 13.3 ± 1.7 years with a mean Cobb angle of 24.4° ± 12.4°). This approach led to the identification of 15 circulating miRNAs that are upregulated in AIS patients who developed a severe scoliosis (Cobb angle ≥45°) at skeletal maturity compared to moderate and mild scoliosis groups (Cobb angle between 25°-44° and <25° respectively). After optimization and the application of Random Forest Models a panel of six miRNAs (miR-1-3p, miR-19a-3p, miR-19b-3p, miR-133b, miR-143-3p, and miR-148b-3p) out of 15 led us to develop an algorithm predicting the risk of developing a severe scoliosis with great accuracy (100%), sensitivity (100%) and specificity (100%). Having a scoliosis predictive bioassay and decision-making tools to predict curve progression in order to find the best treatment plan will undoubtedly transform the orthopedic care system in the field of pediatric scoliosis by integrating innovative precision medicine approaches. In addition, investigation of genes targeted by these miRNAs could fill our gaps in our understanding of AIS pathogenesis and reveal new actionable targets.

Dataset Information

Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis.

Publications

Long noncoding RNA lncAIS downregulation in mesenchymal stem cells is implicated in the pathogenesis of adolescent idiopathic scoliosis.

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