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CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis.
- Source :
-
Cell proliferation [Cell Prolif] 2021 Jun; Vol. 54 (6), pp. e13047. Date of Electronic Publication: 2021 May 07. - Publication Year :
- 2021
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Abstract
- Objectives: Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA).<br />Materials and Methods: The relative expression of circSLC7A2 was significantly lower in OA tissues than it was in matched controls, as shown by real-time quantitative polymerase chain reaction (RT-qPCR). Western blotting, RT-qPCR and immunofluorescence experiments were employed to evaluate the roles of circSLC7A2, miR-4498 and TIMP3. The in vivo role and mechanism of circSLC7A2 were also conformed in a mouse model.<br />Results: circSLC7A2 was decreased in OA model and the circularization of circSLC7A2 was regulated by FUS. Loss of circSLC7A2 reduced the sponge of miR-4498 and further inhibited the expression of TIMP3, subsequently leading to an inflammatory response. We further determined that miR-4498 inhibitor reversed circSLC7A2-knockdown-induced OA phenotypes. Intra-articular injection of circSLC7A2 alleviated in vivo OA progression in a mouse model of anterior cruciate ligament transection (ACLT).<br />Conclusions: The circSLC7A2/miR-4498/TIMP3 axis of chondrocytes catabolism and anabolism plays a critical role in OA development. Our results suggest that circSLC7A2 may serve as a new therapeutic target for osteoarthritis.<br /> (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Apoptosis
Cartilage, Articular metabolism
Cartilage, Articular pathology
Down-Regulation
Gene Expression Regulation
Humans
Mice
MicroRNAs genetics
Osteoarthritis pathology
RNA, Circular analysis
Tissue Inhibitor of Metalloproteinase-3 analysis
Osteoarthritis genetics
RNA, Circular genetics
Tissue Inhibitor of Metalloproteinase-3 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2184
- Volume :
- 54
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell proliferation
- Publication Type :
- Academic Journal
- Accession number :
- 33960555
- Full Text :
- https://doi.org/10.1111/cpr.13047