MiR-217 Regulates SIRT1 Expression and Promotes Inflammatory and Apoptotic Responses in Osteoarthritis

Author:

Papageorgiou Aliki-Alexandra1ORCID,Roussos Athanasios1,Papathanasiou Ioanna12,Balis Charalampos1,Karachalios Theophilos3ORCID,Varitimidis Sokratis E.3,Malizos Konstantinos N.3,Tsezou Aspasia12

Affiliation:

1. Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece

2. Department of Biology, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece

3. Department of Orthopedic Surgery, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41500 Larissa, Greece

Abstract

Previous studies have reported miR-217 uregulation in age-related pathologies. We investigated the impact of miR-217-5p on sirtuin 1 (SIRT1) regulation in human osteoarthritic (OA) chondrocytes. MiR-217 target enrichment analyses were performed using three public databases, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. MiR-217-5p expression levels were quantified in normal and OA chondrocytes. SIRT1 expression levels, nuclear factor kappa-B p65 subunit (NF-κBp65) and p53 acetylation levels, and expression levels of OA-related pro-inflammatory markers [tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), IL-6], pro-apoptotic markers [Bax, pro-caspase 3, cleaved caspase 3] and matrix regulators [matrix metalloproteinase (MMP)-1, MMP-13, MMP-9, Collagen 2 (COL2A1), Aggrecan (ACAN)] were evaluated in miR-217 mimic-treated and/or miR-217 inhibitor-treated OA chondrocytes, with/without subsequent treatment with siRNA against SIRT1 (siSIRT1). MiR-217-5p was upregulated in OA chondrocytes, while target prediction/enrichment analyses revealed SIRT1 as miR-217 target-gene. Deacetylation of NF-κBp65 and p53 in miR-217 inhibitor-treated OA chondrocytes was reversed by siSIRT1 treatment. MiR-217 inhibitor-treated OA chondrocytes showed increased COL2A1, ACAN and decreased IL-1β, IL-6, TNFα, Bax, cleaved caspase 3 and MMPs expression levels, which were reversed following miR-217 inhibitor/siSIRT1 treatment. Our findings highlight the impact of miR-217-5p on SIRT1 downregulation contributing to OA pathogenesis.

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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