• Qian Xiang, Yongzhao Zhao, Shuo Tian, Zhenquan Wu, Jialiang Lin, Shuai Jiang, Longjie Wang, Zhuoran Sun, Chuiguo Sun, and Weishi Li.
• Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
• Spine. 2024 Oct 1.

ObjectiveThis study was aimed to investigate the potential roles of circTMTC1 in the underlying pathophysiological mechanisms of ossification of the ligamentum flavum (OLF).Summary Of Background DataOLF is the primary contributor to thoracic spinal stenosis, which may cause severe neurological symptoms. There is a lack of effective medical therapy for OLF available so far because the exact underlying mechanism of OLF has not been fully elucidated. CircRNAs are a special class of non-coding RNAs and have attracted a growing interest of research in various human diseases recently. Therefore, we explored the potential roles of circRNAs in the underlying pathophysiological mechanisms of OLF.MethodsWe performed RNA-seq analysis to investigate the differentially expression profile of circRNAs in osteogenic differentiation of human LF cells, and identified a key circular RNA circTMTC1 functioned in OLF. Subsequently, we performed a series of experiments to investigate the exact molecular and cellular mechanisms in osteogenic differentiation of human ligamentum flavum cells.ResultsCircTMTC1 is significantly up-regulated during osteogenic differentiation of human LF cells. Mechanistically, we found that circTMTC1 could interact with the RNA binding protein DDX3X and enhance its nucleo-cytoplasmic translocation. An increased cytoplasmic level of DDX3X activated the NLRP3 inflammasome pathway and thus promoted osteogenic differentiation of human ligamentum flavum cells.ConclusionOur findings suggested the circTMTC1-DDX3X-NLRP3 inflammasome signaling plays a pivotal role in osteogenic differentiation of human ligamentum flavum cells, which may provide novel diagnostic and therapeutic strategies for OLF.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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