MicroRNA-26a reduces synovial inflammation and cartilage injury in osteoarthritis of knee joints through impairing the NF-κB signaling pathway.

Zhi Zhao,Xiu-Song Dai,Zheng-Qi Bao,Zhi-Yan Wang,Jian-Zhong Guan

doi:10.1042/bsr20182025

Zhi Zhao, Xiu-Song Dai + Show 3 more

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https://doi.org/10.1042/bsr20182025

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Abstract

Objective: Inflammation is closely implicated in the process of osteoarthritis (OA) and affects disease progression and pain. Herein, the present study explored the effect of microRNA-26a (miR-26a) on the synovial inflammation and cartilage injury in OA, with the involvement with the NF-κB signaling pathway.Methods: Rat models of OA were established by anterior cruciate ligament transection, which were then treated with miR-26a mimics/inhibitors or BMS-345541 (inhibitor of NF-κB pathway). The expression of miR-26a and activator proteins of NF-κB pathway (P-IκBα and P-P65) in synovial tissues was determined. Hematoxylin-eosin (HE) staining was adopted to observe pathological changes of knee joints, synovial tissues, and cartilage of femoral condyle. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of synoviocytes and chondrocytes.Results: Poorly expressed miR-26a and increased protein levels of P-IκBα and P-P65 were identified in synovial tissues of OA rats. Besides, OA rats showed obvious synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle, as well as increased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes. In response to miR-26a mimics, protein levels of P-IκBα and P-P65 were reduced; meanwhile, synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle were ameliorated, with decreased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes.Conclusion: MiR-26a suppressed the activation of the NF-κB signaling pathway, by which mechanism the synovial inflammation and cartilage injury in OA rats were alleviated.

Highlights

Osteoarthritis (OA) is the most common type of arthritis worldwide, and it is a major contributor to pain and disability among the elderly population [1]
In order to observe the role of miR-26a in synovitis and cartilage damage of OA rats, we allocated these rats into five groups with eight rats in each group: normal group, OA group (OA rats without any treatment), negative control (NC) group (OA rats injected with miR-26a NC sequence through knee joint cavity), miR-26a mimics group (OA rats injected with miR-26a mimics through knee joint cavity), and miR-26a inhibitors group (OA rats injected with miR-26a inhibitors through knee joint cavity)
In order to further observe whether miR-26a has effect on synovitis and cartilage damage of OA rats by regulating the NF-B signaling pathway, we allocated the remaining rats into four group (n=8), OA group (OA rats without any treatment), NC group (OA rats injected with miR-26a NC sequence through knee joint cavity), BMS-345541 group (OA rats injected with inhibitor of NF-κB signaling pathway, BMS-345541, through knee joint cavity), and miR-26a inhibitors + BMS-345541 group (OA rats injected with miR-26a inhibitors and inhibitor of NF-κB signaling pathway, BMS-345541, through knee joint cavity)

Summary

Introduction

Osteoarthritis (OA) is the most common type of arthritis worldwide, and it is a major contributor to pain and disability among the elderly population [1]. OA is a frequently occurring disorder involving joint damage, progressive aggravation of the joint architecture, and inadequate healing response [3]. OA is characterized by the loss and injury of articular cartilage in the synovial joints and thinning and loss of cartilage is a critical factor in the development and progression of OA [4, 5]. Multiple researchers emphasized the importance of articular cartilage degeneration and synovitis in OA [7, 8]. Few strategies are available to prevent or treat OA, and multiple molecules and signaling pathways implicated in synovium or cartilage have been studied to understand OA pathogenesis and develop novel therapies [9]

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