LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1β-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p

Abstract

Objective Long non-coding RNA 01534 (LINC01534) is highly expressed in the tissues of patients with osteoarthritis (OA). This study investigated the mechanism of LINC01534 on abnormal metabolic dysfunction in OA chondrocytes induced by interleukin-1β (IL-1β). Methods The quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of LINC01534, aggrecan, collagen II, and matrix metalloproteinase (MMPs) in OA cartilage tissue or OA chondrocyte model induced by IL-1β. The expressions of aggrecan and collagen II in the chondrocyte were detected by Western blot. The levels of tumor necrosis factor–α (TNF-α), IL-8, IL-6, MMP-13, MMP-9, MMP-3, and prostaglandin E2 (PGE2) in chondrocyte were determined by enzyme-linked immunosorbernt assay. Bioinformatics, dual luciferin gene reporting, RNA pulldown, and Northern blot were used to determine the interaction between LINC01534 and miR-140-5p. Results The results showed that LINC01534 was upregulated in both OA cartilage tissue and OA chondrocyte model. In addition, silencing LINC01534 significantly alleviated the inhibitory effect of IL-1β on expressions of aggrecan and collagen II in chondrocytes, and significantly downregulated the expression of matrix metalloproteinases in IL-1β-induced chondrocytes. Meanwhile, silencing LINC01534 also significantly inhibited the productions of proinflammatory factors NO, PGE2, TNF-α, IL-6, and IL-8 in the IL-1β-induced chondrocytes. Furthermore, miR-140-5p was confirmed to be a direct target of LINC01534. More importantly, inhibition of miR-140-5p significantly reversed the inhibitory effect of silencing LINC01534 on abnormal matrix degradation in the IL-1β-induced chondrocyte model of OA. Conclusion Therefore, LINC01534 could promote the abnormal matrix degradation and inflammatory response of OA chondrocytes through the targeted binding of miR-140-5p.

Long noncoding RNA 01534 maintains cancer stemness by downregulating endoplasmic reticulum stress response in colorectal cancer

“…HOTAIR is known as an oncogenic lncRNA in various type of human cancer. 8 However, the LINC01534 literature was limited solely to the inflammatory disease osteoarthritis 10 and we are not aware of any reports on LINC01534 in human cancer.…”

“…A recent report demonstrated high expression of lncRNA 01534 (LINC01534) in the inflammatory disease osteoarthritis, and showed that LINC01534 promotes an inflammatory response through proinflammatory factors, such as TNF‐α and IL‐6 10 . To date, however, we are not aware of any reports that describe LINC01534 in human cancer.…”

PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action

“…Abnormal chondrocyte metabolism is risk factor for OA and can have a direct systemic impact on the joints ( Zheng et al, 2021 ). In the OA setting, the main components of the ECM, aggrecan and type II collagen, are reduced due to inhibition of chondrocyte synthetic activity ( Wei et al, 2021 ). In OA cartilage, the rate of anaerobic glycolysis is increased and changes in key enzymes and glycolytic processes lead to the production and accumulation of excess lactic acid by chondrocytes, creating an acidic microenvironment ( Maneiro et al, 2003 ).…”

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…Long intergenic noncoding RNAs (lincRNAs) have also been involved in the onset and development of OA. In particular, LINC00265, LINC00461, LINC00473, LINC01534, and LINC02288 [ 62 , 63 , 64 , 65 , 66 ] have been demonstrated to promote inflammatory responses by sponging related miRNAs. Among these lincRNAs, LINC00265, LINC00473, and LINC02288 have also been shown to promote apoptosis.…”