Yingjie Wang1, Tian Li2, Qi Yang1, Bin Feng1, Yongbo Xiang1, Zehui Lv1, Xisheng Weng3. 1. Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China. 2. School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China. Electronic address: tian@fmmu.edu.cn. 3. Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China. Electronic address: xshweng@pumch.cams.cn.
Abstract
OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate the occurrence and development of osteoarthritis (OA), whereas the biological roles and mechanisms of the lncRNA THUMPD3-AS1 (THUMPD3 antisense RNA 1) in OA remain still unclear. This study described the role and molecular mechanism of lncRNA THUMPD3-AS1 in regulating OA biology. METHOD: The knee normal and OA cartilage tissues from ten participants were sequenced to reveal the differentially expressed lncRNAs. The interleukin (IL)-1β-stimulated C28/I2 cell served as OA cells. Flow cytometry assays, Western blot, enzyme-linked immunosorbent assays were used for our experiments. RESULTS: The results revealed that lncRNA THUMPD3-AS1 was downregulated in OA cartilage tissues and IL-1β-stimulated chondrocyte cell line. Overexpression of lncRNA THUMPD3-AS1 alleviated cell apoptosis and facilitated inflammatory responses, whereas knockdown had opposite effects. LncRNA THUMPD3-AS1 markedly increased the cyclin E2, cyclin-dependent kinase 4, B-cell lymphoma 2, tumor necrosis factor-α, nitric oxide, and IL-6 levels, and decreased the caspase-3 level. Furthermore, the target proteins of phosphorylation were identified as nuclear factor-κB p65 and mitogen-activated protein kinase p38, which could be indirectly suppressed by lncRNA THUMPD3-AS1 knockdown. CONCLUSION: Our findings highlight the different effects of lncRNA THUMPD3-AS1 on cell apoptosis and inflammatory response, which extend the multiple functions of lncRNA epigenetics in OA biology.
OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate the occurrence and development of osteoarthritis (OA), whereas the biological roles and mechanisms of the lncRNA THUMPD3-AS1 (THUMPD3 antisense RNA 1) in OA remain still unclear. This study described the role and molecular mechanism of lncRNA THUMPD3-AS1 in regulating OA biology. METHOD: The knee normal and OA cartilage tissues from ten participants were sequenced to reveal the differentially expressed lncRNAs. The interleukin (IL)-1β-stimulated C28/I2 cell served as OA cells. Flow cytometry assays, Western blot, enzyme-linked immunosorbent assays were used for our experiments. RESULTS: The results revealed that lncRNA THUMPD3-AS1 was downregulated in OA cartilage tissues and IL-1β-stimulated chondrocyte cell line. Overexpression of lncRNA THUMPD3-AS1 alleviated cell apoptosis and facilitated inflammatory responses, whereas knockdown had opposite effects. LncRNA THUMPD3-AS1 markedly increased the cyclin E2, cyclin-dependent kinase 4, B-cell lymphoma 2, tumor necrosis factor-α, nitric oxide, and IL-6 levels, and decreased the caspase-3 level. Furthermore, the target proteins of phosphorylation were identified as nuclear factor-κB p65 and mitogen-activated protein kinase p38, which could be indirectly suppressed by lncRNA THUMPD3-AS1 knockdown. CONCLUSION: Our findings highlight the different effects of lncRNA THUMPD3-AS1 on cell apoptosis and inflammatory response, which extend the multiple functions of lncRNA epigenetics in OA biology.