MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis

D’Adamo, Stefania; Cetrullo, Silvia; Minguzzi, Manuela; Silvestri, Ylenia; Borzı̀, Rosa Maria; Flamigni, Flavio

doi:10.1155/2017/3720128

Cited by 37 publications

(32 citation statements)

References 168 publications

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“…The maintaining proliferation of chondrocytes is essential for maintaining the integrity of cartilage tissues. miRNAs are a class of non-coding molecules that regulate the expression of target genes and have been shown to participate in the biological regulation of chondrocytes [ 26 ]. For example, Lian et al [ 27 ] showed that miR-128a represses chondrocyte autophagy and exacerbates knee OA by disrupting autophagy related 12 gene.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

et al. 2020

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Recent studies have demonstrated that microRNAs (miRNAs) are involved in many pathological conditions including osteoarthritis (OA). In this study, we aimed to investigate the role of miR-197 in OA and the potential molecular mechanism. The expression levels of miR-197 was detected by quantitative real-time PCR analysis. Cell proliferation and migration abilities were performed by MTT and transwell assays. The concentrations of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were detect using ELISA assay. Furthermore, luciferase reporter and rescue assays were applied to identify the functional target gene of miR-197 in OA. The results showed that miR-197 expression was significantly downregulated in the OA cartilage tissues compared with normal cartilage tissues, accompanied by upregulation of EIF4G2 expression. An inverse correlation was found between EIF4G2 and miR-197 expressions in OA cartilage tissues. Treatment with miR-197 mimics promoted the growth and migration abilities of chondrocytes, while miR-197 inhibitors induced the opposite effects. Furthermore, restoration of miR-197 significantly decreased IL-1β, IL-6, and TNF-α expression, whereas knockdown of miR-197 led to a induction in these inflammatory mediators. Moreover, EIF4G2 was predicted and confirmed as a directly target of miR-197. Overexpressed miR-197 could downregulate EIF4G2 expression in chondrocytes, while miR-197 knockdown could elevate EIF4G2 expression. Additionally, EIF4G2 overexpression reversed the effects of miR-197 mimics on chondrocytes proliferation, migration and inflammation. Taken together, our study demonstrated that miR-197 promotes chondrocyte proliferation, increases migration, and inhibits inflammation in the pathogenesis of OA by targeting EIF4G2, indicating the potential therapeutic targets of the miR-197/EIF4G2 axis for OA treatment.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

et al. 2020

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“…miRNAs are a general class of endogenous noncoding RNAs of 22–25 nucleotides, widely existing in diverse species, and playing essential roles in cell proliferation, immune response, and maintaining homeostasis . miRNAs can control the expression of nearly 30% of protein‐coding genes by targeting a sequence located in the 3′‐untranslated region (3′‐UTR) of the target genes, resulting in cleavage or inhibition of translation and causing profound changes in protein levels .…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

et al. 2019

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Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well‐organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post‐transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA‐based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy‐related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.

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“…MicroRNAs (miRs) belong to the small noncoding RNAs that function as critical gene regulators influencing biological or pathological activities through post-transcriptionally targeting mRNA expression 14 . Thousands of mature miRs were identified in human cells and interfere with the translation of a large variety of human proteins modulating tissue metabolism and deterioration 15 . Accumulating evidence links several microRNA pathways also to OA progression.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12

Lian

et al. 2018

Cell Death Dis

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Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a expression within the articular compartment. Intra-articular injections with miR-128a antisense oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated articular tissue destruction, including cartilage erosion, synovitis, osteophyte formation, and subchondral plate damage. In vitro, miR-128 signaling hindered Atg12 expression, LC3-II conversion, and autophagic puncta formation through targeting the 3′-untranslated region of Atg12. It increased apoptotic programs, diminishing cartilage formation capacity of articular chondrocytes. Inactivating histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR-128a promoter and upregulated miR-128a transcription in inflamed chondrocytes. Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to accelerate miR-128a actions. Interruption of miR-128a signaling attenuated chondrocyte dysfunction and delayed OA development. Our data provide new insights into how miR-128a signaling affects chondrocyte survival and articular cartilage anabolism and highlight the potential of miR-128a targeting therapy to alleviate knee OA.

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MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis

Cited by 37 publications

References 168 publications

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12

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