Aberrant miR-145-5p/β-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis
Publication in refereed journal


摘要Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and -catenin mRNA (CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active -catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T.-P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.
著者Jiajun Zhang, Huanxiong Chen, Ross K. K. Leung, Kwong Wai Choy, Tsz-Ping Lam, Bobby K. W. Ng, Yong Qiu, Jian Q. Feng, Jack C. Y. Cheng, Wayne Y. W. Lee
期刊名稱FASEB Journal
頁次6537 - 6549
關鍵詞bone biopsy, circulating microRNA, primary osteoblasts, serum bone markers

上次更新時間 2021-09-01 於 01:29