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Weiyu Ni Chao Jiang Yizheng Wu Haitao Zhang Lili Wang Jasper H.N. Yik Dominik R. Haudenschild Shunwu Fan Shuying Shen Ziang Hu 《Cell proliferation》2021,54(6)
ObjectivesCircular 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).Materials and MethodsThe 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.ResultscircSLC7A2 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).ConclusionsThe 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. 相似文献
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The strong interest in cell death, and the shift in emphasis from basic mechanisms to translational aspects fostered the launch last year of the new sister journal of Cell Death and Differentiation, named Cell Death and Disease, to reflect its stronger focus towards clinical applications. Here, we review that first year of activity, which reflects an enthusiastic response by the scientific community. On the basis of this, we now launch two novel initiatives, the start of a new section dedicated to cancer metabolism and the opening of a new editorial office in Shanghai. 相似文献