Mechanosensitive lncRNA H19 promotes chondrocyte autophagy, but not pyroptosis, by targeting miR-148a in post-traumatic osteoarthritis

作者：Xuchang Zhou, Hong Cao, Tao Liao, Weizhong Hua, Ruobing Zhao, Dongxue Wang, Huili Deng, Yajing Yang, ShengYao Liu, Guoxin Ni · 发表于：Non-coding RNA Research · 年份：2024 · DOI：10.1016/j.ncrna.2024.07.005 · 被引用次数：10 · 研究领域：Osteoarthritis Treatment and Mechanisms、Cancer-related molecular mechanisms research、Bone and Joint Diseases

Investigating whether mechanosensitive lncRNA H19 can directly target miR-148a to alleviate cartilage damage in post-traumatic osteoarthritis (PTOA). Thirty-two female rats were randomly divided into four groups: Sham-operated group (Sham group, n=8), treadmill running group (R group, n=8), anterior cruciate ligament transection (ACLT) group (ACLT group, n=8), and ACLT + treadmill running group (ACLT + R group, n=8). Histological evaluation was performed to observe the pathological changes in the cartilage of the rat knee. micro-CT was performed to detect the bone morphological changes in the subchondral bone. RT-qPCR and Western-Blot were performed to detect changes in mRNA and protein levels of metabolic and inflammatory factors as well as changes in the expression of lncRNA H19 and miR-148a in cartilage. The Flexcell 5000™ Tension System was used to further validate that lncRNA H19 has mechanosensitivity in vitro. Finally, cell transfection techniques were used to knock down the expression of lncRNA H19 in chondrocytes to validate the regulatory role of lncRNA H19/miR-148a in cartilage metabolism. ACLT combined with treadmill running aggravated the abnormal hyperplasia of subchondral bone in the lateral tibial plateau of the rat knee joint, disturbed the balance of cartilage metabolism, induced cartilage inflammatory response and chondrocyte pyroptosis, which eventually led to cartilage damage and PTOA. Importantly, we found that the expression of lncRNA H19 was significan...