Dataset Information

LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is a common degenerative disease characterized by reducing articular chondrocytes and destruction of joint matrix, it's detailed pathogenesis remains unclear. Emerging evidences have demonstrated that long non-coding RNAs (lncRNAs) are closely related to the progression of OA. This study aims to explore the expression of long non-coding RNA LEMD1 antisense RNA 1 (LEMD1-AS1) in OA tissues and chondrocytes and investigate the possible mechanisms of LEMD1-AS1 in OA, which will provide a new target for the treatment of OA. In our study, LEMD1-AS1 and post-GPI attachment to protein (PGAP1) were lowly expressed, but miR-944 was highly expressed both in OA tissues and in Lipopolysaccharide (LPS) -treated chondrocytes detected by qRT-PCR. Over-expression of LEMD1-AS1 or down-regulation of miR-944 significantly promoted viability, proliferation and inhibited cell apoptosis, cell cycle arrest and inflammatory responses of chondrocytes treated with LPS by CCK-8, EdU, flow cytometry and an ELISA assay. Over-expression of LEMD1-AS1 or down-regulation of miR-944 remarkably increased the protein levels of PCNA, Ki-67, Cyclin A1, Cyclin B1, Cyclin D2 and Bcl-2, while decreasing the protein levels of p27, Bax, Cleaved-caspase-3 and Cleaved-caspase-9 in chondrocytes treated with LPS. LEMD1-AS1 bound to miR-944 and regulated its expression, and PGAP1 presented as a direct target gene of miR-944, which was confirmed by a dual-luciferase reporter assay. Inhibition of PGAP1 partially restored the effects of LEMD1-AS1/miR-944 on the proliferation, cell apoptosis, cell cycle distribution and inflammatory responses of LPS-treated chondrocytes. To conclude, the LEMD1-AS1/miR-944/PGAP1 axis may be a novel therapeutic candidate to target in OA treatment.

SUBMITTER: Li H

PROVIDER: S-EPMC9467614 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.

Li Haitao H Lian Kaihua K Mao Jianguang J Huang Fuguo F Zhang Chunli C Zang Jianguo J

Cell cycle (Georgetown, Tex.) 20220610 19

Osteoarthritis (OA) is a common degenerative disease characterized by reducing articular chondrocytes and destruction of joint matrix, it's detailed pathogenesis remains unclear. Emerging evidences have demonstrated that long non-coding RNAs (lncRNAs) are closely related to the progression of OA. This study aims to explore the expression of long non-coding RNA LEMD1 antisense RNA 1 (LEMD1-AS1) in OA tissues and chondrocytes and investigate the possible mechanisms of LEMD1-AS1 in OA, which will p ...[more]

PMID: 35686740

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Project description:ObjectiveInvestigating whether mechanosensitive lncRNA H19 can directly target miR-148a to alleviate cartilage damage in post-traumatic osteoarthritis (PTOA).MethodsThirty-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.ResultsACLT 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 significantly downregulated in the cartilage of the ACLT + R group. Bioinformatics analysis revealed that miR-148a may be a direct target of lncRNA H19. Subsequently, we focused on the mechanosensitive of lncRNA H19. Subsequently, moderate-intensity mechanical tension stress reversed the expression of lncRNA H19 and autophagy-related factors in inflammatory chondrocytes, while miR-148a showed an opposite expression trend, demonstrating that mechanosensitive lncRNA H19 may be involved in regulating the chondrocyte inflammatory response by targeting miR-148a and activating autophagy. Cell transfection experiments revealed that lncRNA H19 knockdown upregulated miR-148a expression and significantly inhibited the autophagy level of chondrocytes without significant alteration of chondrocyte pyroptosis, which in turn exacerbated the inflammatory response of chondrocytes.ConclusionsMechanosensitive lncRNA H19 can promote chondrocyte autophagy rather than pyroptosis by targeting miR-148a, thus alleviating cartilage damage in PTOA. LncRNA H19 may be a potential therapeutic target for PTOA.

Dataset Information

LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.

Publications

LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.

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