Premium
miR‐877‐5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1
Author(s) -
Zhu Shaobo,
Deng Yu,
Gao Hui,
Huang Kaiyuan,
Nie Zhongjie
Publication year - 2020
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3246
Subject(s) - in vivo , chondrocyte , in vitro , cartilage , foxm1 , microbiology and biotechnology , apoptosis , microrna , viability assay , chemistry , medicine , biology , gene , biochemistry , anatomy , cell cycle
Background The present study aimed to investigate whether forkhead box M1 (FOXM1), as a putative target of miR‐877‐5p, participated in interleukin (IL)‐1β‐induced cartilage degeneration in experimental osteoarthritis (OA) models in vitro and in vivo.Methods In vitro and in vivo models of OA were established using IL‐1β treated primary mouse chondrocytes and anterior cruciate ligament transection (ACLT) operation in mice. miR‐877‐5p mimics or agomir‐miR‐877‐5p were used as therapeutic agents in both in vitro and in vivo models of OA. Cell viability and apoptosis were evaluated using cell counting kit‐8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining, respectively. A quantitative reverse transcriptase‐polymerase chain reaction and western blotting were used to measure gene and protein expression, respectively. Results FOXM1 was up‐regulated in IL‐1β‐stimulated chondrocytes and the proximal tibia of ACLT‐operated mice. Bioinformatics algorithms deduced a highly conserved sequence in the 3'‐UTR of FOXM1 that could be bound with miR‐877‐5p. A luciferase assay indicated that miR‐877‐5p directly targeted the 3'‐UTR of FOXM1. Overexpression of miR‐877‐5p could reduce protein expression of FOXM1 in chondrocytes. Concurrently, IL‐1β‐evoked up‐regulation of FOXM1 protein expression was neutralized in chondrocytes following transfection with miR‐877‐5p mimics. miR‐877‐5p mimics or agomir‐miR‐887‐5p could inhibit IL‐1β‐induced inflammation in both in vitro and in vivo models of OA. miR‐877‐5p might have beneficial effects on the synthesis of cartilage matrix via the promotion of SRY‐box transcription factor 9 and type II collagen expression and inhibition of matrix metalloproteinase 9 expression. Conclusions miR‐877‐5p can improve chondrocyte function in both in vivo and in vitro models of OA, based on post‐transcriptional repression of FOXM1 as a postulated molecular mechanism.