MicroRNA‑195‑5p inhibitor prevents the development of osteoarthritis by targeting REGγ

Shu,Yang; Long,Junpeng; Guo,Weixiong; Ye,Wei

doi:10.3892/mmr.2019.10124

MicroRNA‑195‑5p inhibitor prevents the development of osteoarthritis by targeting REGγ

Authors:
- Yang Shu
- Junpeng Long
- Weixiong Guo
- Wei Ye
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Affiliations: Department of Orthopedics, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei 430015, P.R. China, Department of Anesthesiology, Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, Hubei 430074, P.R. China, Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: April 3, 2019 https://doi.org/10.3892/mmr.2019.10124
Pages: 4561-4568
Copyright: © Shu 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 common inflammatory joint disease. MicroRNAs (miRNAs/miRs) have been reported to be involved in the pathogenesis of OA; however, the role of miRNAs in OA remains largely unexplained. The purpose of the present study was to investigate the expression and role of miR‑195‑5p in OA, and to further explore the mechanism. The expression level of miR‑195‑5p was measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). TargetScan and a luciferase reporter assay were used to reveal the associations between miR‑195‑5p and REGγ (also known as PSME3). To investigate the role of miR‑195‑5p in OA, a cell model of OA was established by treating ATDC5 cells with lipopolysaccharide (LPS). Then an MTT assay was conducted to detect cell proliferation ability, and an Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis detection kit was used to measure cell apoptosis. In addition, the levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α were determined using ELISA. Furthermore, gene and protein expression was measured via RT‑qPCR and western blot assay, respectively. The results revealed that miR‑195‑5p was significantly upregulated in the articular cartilage tissues of patients with OA and in LPS stimulated ATDC5 cells. REGγ was a direct target of miR‑195‑5p. The repressed cell proliferation ability and enhanced cell apoptosis of ATDC5 cells induced by LPS were reversed by miR‑195‑5p downregulation. Furthermore, LPS stimulation significantly upregulated the levels of IL‑1β, IL‑6 and TNF‑α, while miR‑195‑5p downregulation markedly reduced the expression of inflammatory factors induced by LPS. The results also revealed that a miR‑195‑5p inhibitor inhibited the LPS induced repression of the Wnt/β‑catenin signaling pathway and activation of nuclear factor (NF)‑κB signaling pathway in ATDC5 cells. Notably, the results of the present study also indicated that all of the effects of the miR‑195‑5p inhibitor on ATDC5 cells were reversed by REGγ silencing. In conclusion, the results indicated that the miR‑195‑5p inhibitor served a protective role in OA by inhibiting chondrocyte apoptosis and inflammatory responses by regulating the Wnt/β‑catenin and NF‑κB signaling pathways.

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