Upregulation of microRNA-125b-5p is involved in the pathogenesis of osteoarthritis by downregulating SYVN1

Abstract

Abstract. Osteoarthritis (OA) is a degenerative disease characterized by deterioration of articular cartilage. The aim of this study was to identify and characterize the expression of microRNA-125b-5p (miR-125b-5p) in normal and OA synovial cells, and to determine its role in OA pathogenesis. First, the levels of miR-125b-5p and synoviolin 1 (SYVN1) were detected among normal, mild OA and severe OA groups with the use of quantitative PCR. Computational analysis was used to search for the target of the miR-125b-5p, and luciferase reporter assay system was used to validate SYVN1 as the target gene of miR-125b-5p. Then the SYVN1 expression level of cells transfected with miR-125b-5p mimics or inhibitors was estimated using quantitative PCR and western blotting. Finally, MTT assay was employed to estimate the effect of miR-125b-5p on apoptosis. We enrolled 36 participants consisting of 12 normal control, 12 mild OA and 12 severe OA, furthermore, we performed quantitative PCR to detect the levels of miR-125b-5p and SYVN1 among those groups, and found that miR-125b-5p was expressed at highest level in severe OA compared with normal control and mild OA groups, while SYVN1 was expressed at the lowest level in severe OA. Additionally, we identified that SYVN1 is a target of miR-125b-5p by using computational analysis and luciferase assay. Transfection with miR-125b-5p mimic or inhibitor was employed to investigate the effect of miR-125b-5p on expression of SYVN1 in synovial cells, and synovial cell viability and apoptosis, and the results showed that miR-125b-5p mimics significant decreased the expression of SYVN1, a substantially promoted apoptosis of synovial cells, while miR-125b-5p inhibitors remarkably increased the level of SYVN1, and substantially suppressed apoptosis of synovial cells. The data suggested that miR125b-5p promoted apoptosis of synovial cells through targeting SYVN1 gene, with important implication for validating miR-125b-5p as a potential target for OA therapy.

LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a vital role in proliferation, apoptosis and autophagy in osteoarthritis

“…Synoviolin 1 (SYVN1) was associated with ER stress, chronic inflammation, and vascular overgrowth in diabetic retinopathy (DR) [37,38]. Overexpression of miR-125b-5p was associated with the pathogenesis of osteoarthritis by down-regulation of SYVN1 [38], reflecting that SYVN1 was closely associated with OA. Besides, in our study, SYVN1 was first identified as a target of miR-34a-5p using RIP and luciferase reporter assay.…”

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

“…Interestingly, reduced miR-29 is also implicated in fibrogenesis of systemic sclerosis, an autoimmune rheumatic disease (109). miR-125b-5p expression increases with OA severity (110), and miR-125b-5p overexpression inhibits OA synovial cell proliferation and promotes apoptosis by targeting synoviolin (SYVN1), suggesting miR-125b-5p upregulation is an attempt to attenuate synovial hyperplasia and fibrosis (110). Thus, miR-29 family miRs and miR-125b-5p expression may be part of an effort to maintain normal synovial function rather than contribute to pathologic OA disease progression.…”

Insights into Inflammatory Priming of Adipose-Derived Mesenchymal Stem Cells: Validation of Extracellular Vesicles-Embedded miRNA Reference Genes as A Crucial Step for Donor Selection

“…Refining our analysis only for the top five expressed miRNAs, miR-24-3p is shown to be involved in downregulating MMP1 and MMP13 expression by targeting senescence marker p16INK4a [75]. miR-125b-5p was shown to promote apoptosis of synovial cells through targeting synoviolin 1 [76]. miR-222-3p may significantly suppress apoptotic death in chondrocytes by down-regulating HDAC4 and MMP13 levels and reducing cartilage destruction [77].…”