MicroRNA-486 promotes a more catabolic phenotype in chondrocyte-like cells by targeting SIRT6
| Autor: | Zandong Zhao, Jing Bingfei, Jie Yang, Xiaojun Liang, Yunping Zhou |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
SIRT6 Articular cartilage Diseases of the musculoskeletal system Osteoarthritis SW1353 cell line Biology Cartilage degradation Chondrocyte 03 medical and health sciences 0302 clinical medicine microRNA medicine Orthopedics and Sports Medicine Catabolism Arthritis miR-486 medicine.disease Phenotype Cell biology 030104 developmental biology medicine.anatomical_structure RC925-935 030220 oncology & carcinogenesis Surgery Chondrocyte catabolic phenotype |
| Zdroj: | Bone & Joint Research Bone & Joint Research, Vol 10, Iss 7, Pp 459-466 (2021) |
| ISSN: | 2046-3758 |
| DOI: | 10.1302/2046-3758.107.bjr-2019-0251.r4 |
| Popis: | Aims Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. Methods The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype. Results Compared with osteonecrosis, the expression of miR-486 was significantly upregulated in cartilage from subjects with severe OA. In addition, overexpressed miR-486 promoted a catabolic phenotype in SW1353 cells by upregulating the expressions of ADAMTS4 and MMP-13 and down-regulating the expressions of COL2A1 and ACAN. Conversely, inhibition of miR-486 had the opposite effect. Furthermore, overexpression of miR-486 significantly inhibited the expression of SIRT6, confirming that SIRT6 is a direct target of miR-486. Moreover, SW1353 cells were transfected with small interfering RNA (si)-SIRT6 and it was found that SIRT6 was involved in and inhibited miR-486-induced changes to SW1353 gene expression. Conclusion Our results indicate that miR-486 promotes a catabolic phenotype in SW1353 cells in OA by targeting SIRT6. Our findings might provide a potential therapeutic target and theoretical basis for OA. Cite this article: Bone Joint Res 2021;10(7):459–466. |
| Databáze: | OpenAIRE |
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