miR‐877‐5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1

Abstract

Background: The present study aimed to investigate whether forkhead box M1 (FOXM1), as a putative target of miR-877-5p, participated in interleukin (IL)-1βinduced 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 transcriptasepolymerase 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.

microRNA-877-5p exerts tumor-suppressive functions in prostate cancer through repressing transcription of forkhead box M1

“…Recently, it is observed that FOXM1 expression has a potential prognostic value for prostate cancer, however, there is some evidence verifying that miR-877-5p can improve chondrocyte function of experimental osteoarthritis(OA) by targeting FOXM1 as a postulated molecular mechanism [ 18 , 39 ]. Then, the relationship between miR-877-5p and FOXM1 caught our attention, we speculated miR-877-5p may bind to FOXM1 to achieve the results of regulating cell biological function in prostate cancer.…”

“…The relationship between miR-877-5p and FOXM1 were conducted in several studies. For example, miR-877-5p can affect cellular activities by regulating the transcription of forkhead box M1 (FOXM1) in osteoarthritis models [ 18 ]. Further, studies have also pointed out miR-877-5p suppresses cell proliferation through FOXM1 in gastric cancer [ 19 ].…”

MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression

“…miR-25 [ 15 ], miR-33-5p [ 16 ], miR-221, and miR-15b [ 17 ] have been revealed to act on corresponding targets, thus affecting the balance between bone formation and resorption, and therein regulating osteoblast differentiation. miR-877-5p is frequently downregulated in various cancers [ 18 – 20 ], and particularly, miR-877-5p has an alleviating impact on osteoarthritis chondrocytes [ 21 ]. In addition, miR-877-3p promotes osteoblast differentiation of MC3T3-E1 cells by targeting Smad7 [ 22 ].…”