MicroRNA-322 Attenuates Cartilage Matrix Degradation in Osteoarthritis via Direct Suppression of TRAF3

Author:

Wang Jirong1ORCID,Chai Lan2,Tang Ying1,Wang Guofu1,Bao Yizhong1,Ma Bo3

Affiliation:

1. Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, China

2. Department of Rheumatology and Immunology, Zhejiang Hospital, Hangzhou, China

3. Department of Breast Surgery, Zhejiang Hospital, Hangzhou, China

Abstract

Objective Osteoarthritis (OA) is a degenerative joint disease. A growing number of studies have shown that microRNAs (miRNAs) play an important role in the pathogenesis of OA. However, the specific function of miR-322 in OA is unknown. This study was aimed to explore the ability of miR-322 in the cartilage matrix degradation and the mechanism in OA. Methods Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect miR-322 expression in cartilage and OA-associated gene expression in chondrocytes treated with miR-322 mimics/inhibitors or interleukin (IL)-1β, respectively. The targets of miR-322 were analyzed using software and the luciferase reporter experiment. In vivo, intra-articular injection of miR-322 mimics was administered at the knee of DMM mice. After 12 weeks, the knee joints of mice were collected for histological analysis. Results The expression of miR-322 was decreased in knee cartilage of DMM mice and was significantly reduced by IL-1β. miR-322 mimics inhibited IL-1β-induced extracellular matrix degradation, as evidenced by higher expression of Col2α1 and Aggrecan, and lower expression of Adamts5, MMP3, and MMP13. In contrast, miR-322 inhibitor promoted extracellular matrix degradation of chondrocytes. TRAF3 was the predicted target of miR-322 from databases. Luciferase reporter assay verified the targeting relationship between miR-322 and TRAF3. The effect of miR-322 on extracellular matrix degradation was partially reversed by overexpression of TRAF3. In addition, H&E and Safranin-O fast green staining assays in OA mouse models showed that miR-322 mimics attenuated the progression of OA in vivo. Conclusions miR-322 suppressed chondrocytes matrix degradation and alleviated OA cartilage injury via inhibition of the TRAF3.

Publisher

SAGE Publications

Subject

Physical Therapy, Sports Therapy and Rehabilitation,Biomedical Engineering,Immunology and Allergy

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