Inhibition of Long Non-coding RNA CTD-2574D22.4 Alleviates LPS-induced Apoptosis and Inflammatory Injury of Chondrocytes

• Published in: Current pharmaceutical design Vol. 25; no. 27; p. 2969
• Main Authors: Li, Lisong, Zhang, Lianfang, Zhang, Yong, Jiang, Dinghua, Xu, Wu, Zhao, Haiyue, Huang, Lixin
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2019
• Subjects: Aged; Animals; Apoptosis; Cell Line; Chondrocytes - drug effects; Gene Knockdown Techniques; Humans; Inflammation; Lipopolysaccharides; Mice; Middle Aged; RNA, Long Noncoding - genetics; LncRNA; CTD-2574D22.4; apoptosis; cartilage degeneration; inflammatory injury; Osteoarthritis
• ISSN: 1873-4286
• DOI: 10.2174/1381612825666190801141801

Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration. Long non-coding RNAs (lncRNAs) have been associated with inflammatory diseases, including OA. Here, we investigated the potential molecular role of lncRNAs in OA pathogenesis.
ATDC5 cells were treated with lipopolysaccharides (LPS), and qPCR was used to identify and determine expression of potential lncRNAs involved in LPS-induced chondrocyte injury. Cell viability, apoptosis, and expression of cartilage-related genes and inflammatory cytokines were assessed after CTD-2574D22.4 knockdown.
After LPS stimulation, CTD-2574D22.4 was found to be the second highest up-regulated gene, and the enhanced expression was validated in OA chondrocytes. Moreover, CTD-2574D22.4 inhibition significantly rescued cell viability, suppressed by LPS stress, and markedly attenuated LPS-induced apoptosis. The expression of cartilage-degrading enzymes MMP-13 and ADAMTS-5 were increased, while type II collagen was reduced after LPS treatment. This trend was largely reversed by CTD-2574D22.4 knockdown. Additionally, mRNA and protein levels of key inflammatory cytokines (TNF-a, IL-6, and IL-1β) were significantly elevated in the LPS group and partially relieved upon CTD-2574D22.4 knockdown.
CTD2574D22.4 knockdown ameliorates LPS-induced cartilage injury by protecting chondrocytes from apoptosis via anti-inflammation and anti- cartilage-degrading pathways. Thus, CTD2574D22.4 might be a potential diagnostic and therapeutic target for OA.