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

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)-1ß, 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-1ß. miR-322 mimics inhibited IL-1ß-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.