Knockdown of hsa_circ_0037658 inhibits the progression of osteoarthritis via inducing autophagy

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RESEARCH ARTICLE

Knockdown of hsa_circ_0037658 inhibits the progression of osteoarthritis via inducing autophagy Cong Sui1 · Debao Liu1 · Yukang Que1 · Shenglin Xu1 · Yong Hu1 Received: 9 July 2020 / Accepted: 20 September 2020 © Japan Human Cell Society 2020

Abstract Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease that can result in chronic pain and functional disability. Circular RNAs (CirRNAs) are known to be involved in OA. It was reported that hsa_circ_0037658 was notably upregulated in OA tissues; however, the biological role of hsa_circ_0037658 in OA remains unclear. To investigate the function of hsa_circ_0037658 in OA, CHON-001 cells were treated with IL-1β. The effect of hsa_circ_0037658 knockdown on cell growth was tested by CCK-8 and immunofluorescence staining. In addition, the correlation between hsa_circ_0037658 and autophagy was explored by LC3 staining and western blot. The results indicated that hsa_circ_0037658 was significantly upregulated in IL-1β-treated CHON-001 cells. The silencing of hsa_circ_0037658 could protect CHON-001 cell injury against IL-1β. Moreover, hsa_circ_0037658 shRNA reversed IL-1β-induced cell growth inhibition via inducing cell autophagy. Furthermore, knockdown of hsa_circ_0037658 notably alleviated the symptom of OA in vivo. To sum up, knockdown of hsa_circ_0037658 suppressed the progression of OA via inducing autophagy. Thus, hsa_circ_0037658 might serve as a potential target for the treatment of OA. Keywords  OA · hsa_circ_0037658 · Autophagy

Introduction Osteoarthritis (OA) is the most common form of arthropathy in elderly individuals all over the world which is characterized by local inflammation, articular cartilage damage, and degradation of the cartilage [1, 2]. The risk factors of OA are majorly joint damage, joint, age, and genetic factors [3–5]. Current therapeutic strategies for OA are aimed at symptomatic control, rather than disease modification; however, the therapeutic effect still remains limited [6]. Therefore, it is urgent to find novel therapeutic strategies for the treatment of OA. Circular RNAs (CircRNAs) are a class of endogenous RNA molecules with a stable closed-loop structure [7, 8]. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1357​7-020-00440​-9) contains supplementary material, which is available to authorized users. * Yong Hu [email protected] 1



Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, China

CircRNAs play important roles in cell biological functions such as protein synthesis, gene expression, and post-transcriptional modification [9, 10]. In addition, the abnormal expression of circRNAs was closely correlated with the occurrence and development of OA [11, 12]. Furthermore, circRNAs mainly played a potential role in chondrocyte proliferation, apoptosis and inflammation in OA [13, 14]. It is reported that hsa_circ_0037658 was notably upregulated in OA [15]; however, the role of hsa

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