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  • Title: Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR-296-3p/PTEN axis.
    Author: Zhou Z, Ma J, Lu J, Chen A, Zhu L.
    Journal: J Cell Physiol; 2021 May; 236(5):3521-3535. PubMed ID: 33037617.
    Abstract:
    Circular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain-of-function and loss-of-function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR-296-3p and miR-296-3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno-associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)-induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR-296-3p and regulating the miR-296-3p-PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM-induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR-296-3p-PTEN pathway. It provides a potential target for developing effective interventions in treating OA.
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