LncRNAs in Osteoarthritis

Okuyan, Hamza Malik; Begen, Mehmet A.

doi:10.1016/j.cca.2022.05.030

Cited by 26 publications

(16 citation statements)

References 134 publications

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“…It has been reported that in addition to protein-coding genes, large non-coding RNAs function as gene regulators during the OA progression [ 40 , 41 ]. MiRNA processing is also regulated specifically for OA.…”

Section: Discussionmentioning

confidence: 99%

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression

et al. 2023

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Objectives Increasing evidence have demonstrated the N6-methyladenosine (m6A) plays critical roles in osteoarthritis (OA) progression, but the role of m6A in OA has not been completely illuminated. Herein, we investigated the function and underlying mechanism of m6A demethylase fat mass and obesity-associated protein (FTO) in OA progression. Materials and methods The FTO expression was detected in mice OA cartilage tissues and lipopolysaccharide (LPS)-stimulated chondrocytes. Gain-of-function assays was used to evaluate the role of FTO in OA cartilage injury in vitro and in vivo. The miRNA-sequencing, RNA-binding protein immunoprecipitation (RIP), luciferase reporter assay, and in vitro pri-miRNA processing assays were conducted to confirm that FTO modulated the pri-miR-3591 process in an m6A-dependent manner and then the binding sites of miR-3591-5p with PRKAA2. Results FTO was outstandingly downregulated in LPS-stimulated chondrocytes and OA cartilage tissues. FTO overexpression enhanced the proliferation, suppressed apoptosis, and decreased degradation of extracellular matrix in LPS-induced chondrocytes, whereas FTO knockdown contributed to the opposite effects. In vivo animal experiments showed that FTO overexpression markedly alleviated OA mice cartilage injury. Mechanically, FTO-mediated m6A demethylation of pri-miR-3591 leaded to a maturation block of miR-3591-5p, which relieved the inhibitory effect of miR-3591-5p on PRKAA2 and then promoted the increase of PRKAA2, thereby alleviating OA cartilage damage. Conclusions Our results attested that FTO alleviated the OA cartilage damage by mediating FTO/miR-3591-5p/PRKAA2 axis, which provided fresh insights into the therapeutic strategies for OA.

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Section: Discussionmentioning

confidence: 99%

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression

et al. 2023

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“…Long non-coding RNAs (lncRNAs) are a subclass of non-coding RNAs (ncRNAs), with a length of approximately 200 nucleotides [ 13 ]. Previous studies have demonstrated the participation of lncRNAs in many human diseases, including OA [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA AC006064.4–201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1

Shen

Gao²,

Huang³

et al. 2023

Biomark Res

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Background Osteoarthritis (OA) is the most prevalent age-related disease in the world. Chondrocytes undergo an age-dependent decline in their proliferation and synthetic capacity, which is the main cause of OA development. However, the intrinsic mechanism of chondrocyte senescence is still unclear. This study aimed to investigate the role of a novel long non-coding RNA (lncRNA), AC006064.4–201 in the regulation of chondrocyte senescence and OA progression and to elucidate the underlying molecular mechanisms. Methods The function of AC006064.4–201 in chondrocytes was assessed using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) and β-galactosidase staining. The interaction between AC006064.4–201 and polypyrimidine tract-binding protein 1 (PTBP1), as well as cyclin-dependent kinase inhibitor 1B (CDKN1B), was evaluated using RPD-MS, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice models were used to investigate the role of AC006064.4–201 in post-traumatic and age-related OA in vivo. Results Our research revealed that AC006064.4–201 was downregulated in senescent and degenerated human cartilage, which could alleviate senescence and regulate metabolism in chondrocytes. Mechanically, AC006064.4–201 directly interacts with PTBP1 and blocks the binding between PTBP1 and CDKN1B mRNA, thereby destabilizing CDKN1B mRNA and decreasing the translation of CDKN1B. The in vivo experiments were consistent with the results of the in vitro experiments. Conclusions The AC006064.4–201/PTBP1/CDKN1B axis plays an important role in OA development and provides new molecular markers for the early diagnosis and treatment of OA in the future. Graphical Abstract Schematic diagram of AC006064.4–201 mechanism. A schematic diagram of the mechanism underlying the effect of AC006064.4–201

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“…Inhibition PI3K/AKT/mTOR signaling pathway involved in cellular autophagy by NOV/CCN3 ameliorated the IL-1βinduced matrix catabolism and in ammatory and promoted the expression of Atg5 and Beclin1 for cartilage protection 17,18,19 . In addition, epigenetics modi cation (microRNA, lncRNA) regulated autophagy pathway to affect the develop of osteoarthritis 20,21,22,23 . MiR-155, miR-27a 24 , miR-34a, miR-449a, miR-9, miR-140-5p, miR-20, miR-146a and miR-149 regulated osteoarthritis generation and development by targeting autophagy-related genes (SIRT1, ULK1, FUT1, ATG10, BCL2 and so on).…”

Section: Introductionmentioning

confidence: 99%

Autophagy-related genes and pathways was associated with osteoarthritis pathogenesis

Guan

Guo

et al. 2023

Preprint

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Background: Patients with osteoarthritis have musculoskeletal-related chronic disability, leading to the high pain intensity. Explaining the molecular mechanisms of osteoarthritis is critial for the diagnosis and cure. Therefore, This research aimed to find key candidate genes involved in osteoarthritis pathogenesis. Methods: We identified differentially expressed genes by integrating multiple microarry datasets in cartilage (GSE43923, GSE113825, GSE129147 and GSE169077). Functional enrichment analysis and protein-protein interaction analysis were performed. Results: We identified sixty-six significantly expression genes (56 up-regulated and 10 down-regulated). Through functional enrichment analysis and protein-protein interaction analysis, we found that the biological process of these genes was enriched in focal adhesion, ECM-receptor interaction and PI3K-Akt signaling, which were closely related with autophagy. Moreover, ceRNA network showed that thirty-four DEGs, including ECM-receptor interaction-related genes (COL4A1, COL4A2 and COL1A2, LAMB1 an THBS2), exist competing endogenous regulating network mediated by 7 lncRNAs and 8 miRNAs. Furthermore, differentially expressed autophagy-related genes (CCL2, CDKN1A, CXCR4, DAPK1, DLC1, FAS, HSPA8, MYC and SERPINA1) were remarkably identified to interact with multiple of the common DEGs in ECM-receptor interaction and PI3K-Akt signaling pathway, suggesting that autophagy plays important role in osteoarthritis pathogenesis by regulating ECM-receptor interaction and PI3K-Akt signaling pathway. Conclusions: This multiple transcriptome analysis identifies ECM-receptor interaction and PI3K-Akt signaling pathway related to osteoarthritis pathogenesis by regulating autophagy and participating in ceRNA network.

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LncRNAs in Osteoarthritis

Cited by 26 publications

References 134 publications

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression

FTO-mediated m6A demethylation of pri-miR-3591 alleviates osteoarthritis progression

LncRNA AC006064.4–201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1

Autophagy-related genes and pathways was associated with osteoarthritis pathogenesis

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