MicroRNA‑93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF‑κB signaling pathway

Ding,Yanjie; Wang,Laifang; Zhao,Qing; Wu,Zhenzhen; Kong,Lingli

doi:10.3892/ijmm.2018.4033

MicroRNA‑93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF‑κB signaling pathway

Authors:
- Yanjie Ding
- Laifang Wang
- Qing Zhao
- Zhenzhen Wu
- Lingli Kong
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Affiliations: Department of Rheumatology and Immunology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
Published online on: December 18, 2018 https://doi.org/10.3892/ijmm.2018.4033
Pages: 779-790
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a serious disease of the articular cartilage, and inflammation has been implicated in its pathogenesis. Previously, microRNAs (miRNAs) have been proposed as novel regulators of inflammation, however, the functional role of microRNAs in regulating inflammation in OA remains to be fully elucidated. The aim of the present study was to investigate the roles of miRNAs in OA inflammation and the underlying molecular mechanism. Firstly, the miRNA expression patterns were analyzed in the articular cartilage tissues from experimental OA mice using an miRNA microarray. miRNA (miR)‑93 was identified with particular interest due to its reported effects on apoptosis and inflammation suppression. Subsequently, the expression of miR‑93 was further validated in the articular cartilage tissues of OA mice and lipopolysaccharide (LPS)‑stimulated primary chondrocytes. Using this LPS‑induced chondrocyte injury model, the overexpression of miR‑93 enhanced cell viability, improved cell apoptosis and attenuated the inflammatory response, as reflected by reductions in pro‑inflammatory cytokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6. In addition, Toll‑like receptor 4 (TLR4), an important regulator of the nuclear factor‑κB (NF‑κB) signaling pathway, was identified as a direct target of miR‑93 in chondrocytes. Furthermore, the restoration of TLR4 markedly abrogated the inhibitory effects of miR‑93 on the chondrocyte apoptosis and inflammation induced by LPS. In addition, the overexpression of miR‑93 by agomir‑miR‑93 significantly inhibited the levels of pro‑inflammatory cytokines and cell apoptosis, whereas antagomir‑93 exacerbated apoptosis and inflammation in vivo. Taken together, the results of the study suggested that miR‑93 may be a promising therapeutic target for the treatment of human OA.

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