{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["73(3)"],"submitter":["Endisha H"],"funding":["Canadian Institute of Health Research Operating grant","Canada Research Chairs"],"pubmed_abstract":["<h4>Objective</h4>MicroRNA-34a-5p (miR-34a-5p) expression is elevated in the synovial fluid of patients with late-stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR-34a-5p in OA pathogenesis.<h4>Methods</h4>Expression of miR-34a-5p was determined in joint tissues and human plasma (n = 71). Experiments using miR-34a-5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast-like synoviocytes (FLS) (n = 7-9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high-fat diet and subjected to DMM (n = 11). Wild-type (WT) mice (n = 9) and miR-34a-knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t-test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes.<h4>Results</h4>Expression of miR-34a-5p was significantly increased in the plasma, cartilage, and synovium of patients with late-stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR-34a-5p expression was significantly increased in obese patients with late-stage OA, and in the plasma and knee joints of mice fed a high-fat diet. In human OA chondrocytes and FLS, miR-34a-5p mimic increased key OA pathology markers, while miR-34a-5p ASO improved cellular gene expression. Intraarticular miR-34a-5p mimic injection induced an OA-like phenotype. Conversely, miR-34a-5p ASO injection imparted cartilage-protective effects in the DMM and high-fat diet/DMM models. The miR-34a-KO mice exhibited protection against DMM-induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR-34a-5p signaling network.<h4>Conclusion</h4>Our findings provide comprehensive evidence of the role and therapeutic potential of miR-34a-5p in OA."],"journal":["Arthritis & rheumatology (Hoboken, N.J.)"],"pagination":["426-439"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7986901"],"repository":["biostudies-literature"],"pubmed_title":["MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis."],"pmcid":["PMC7986901"],"pubmed_authors":["Younan C","Rossomacha E","Krawetz R","Kapoor M","Lively S","Potla P","Endisha H","Datta P","Sharma A","Rockel JS","Gandhi R","Jurisica I","Nakamura S","Ali SA","Shestopaloff K","Tavallaee G","Mahomed NN"],"additional_accession":[]},"is_claimable":false,"name":"MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis.","description":"<h4>Objective</h4>MicroRNA-34a-5p (miR-34a-5p) expression is elevated in the synovial fluid of patients with late-stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR-34a-5p in OA pathogenesis.<h4>Methods</h4>Expression of miR-34a-5p was determined in joint tissues and human plasma (n = 71). Experiments using miR-34a-5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast-like synoviocytes (FLS) (n = 7-9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high-fat diet and subjected to DMM (n = 11). Wild-type (WT) mice (n = 9) and miR-34a-knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t-test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes.<h4>Results</h4>Expression of miR-34a-5p was significantly increased in the plasma, cartilage, and synovium of patients with late-stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR-34a-5p expression was significantly increased in obese patients with late-stage OA, and in the plasma and knee joints of mice fed a high-fat diet. In human OA chondrocytes and FLS, miR-34a-5p mimic increased key OA pathology markers, while miR-34a-5p ASO improved cellular gene expression. Intraarticular miR-34a-5p mimic injection induced an OA-like phenotype. Conversely, miR-34a-5p ASO injection imparted cartilage-protective effects in the DMM and high-fat diet/DMM models. The miR-34a-KO mice exhibited protection against DMM-induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR-34a-5p signaling network.<h4>Conclusion</h4>Our findings provide comprehensive evidence of the role and therapeutic potential of miR-34a-5p in OA.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-18T21:43:20.976Z","creation":"2025-04-07T09:33:59.468Z"},"accession":"S-EPMC7986901","cross_references":{"pubmed":["33034147"],"doi":["10.1002/art.41552"]}}