Circular RNA circ_0114876 regulates osteoarthritis through upregulating ADAM10 via targeting miR-1227-3p |
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| Affiliation: | 2. Department of Orthopedic, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou Province 550003, China;3. Department of Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan Province 410208, China;1. Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan;2. Department of Diagnostic Pathology, Graduate School of Medicine, Osaka City University, Osaka, Japan;3. Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Osaka, Japan;1. Department of Transfusion Medicine, Histocompatibility and Molecular Biology, Jaypee Hospital, Noida, UP 201301, India;2. Department of Histocompatibility and Molecular Biology, Jaypee Hospital, Noida,UP 201301, India;3. Department of Transfusion Medicine, Jaypee Hospital, Noida, UP 201301, India;4. Kidney Transplant Programme, Department of Urology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;5. Department of Nephrology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;1. Department of Respiratory Medicine, Tokyo Women''s Medical University, Tokyo, Japan;2. Department of Infectious Diseases, Tokyo Women''s Medical University, Tokyo, Japan;3. Department of Infection Prevention and Control, Tokyo Women''s Medical University, Tokyo, Japan;4. Department of Pharmacy, Tokyo Women''s Medical University, Tokyo, Japan;5. Department of Urology, Tokyo Women''s Medical University, Tokyo, Japan;6. Department of General Medicine, Tokyo Women''s Medical University, Tokyo, Japan;7. Department of Surgery, Institute of Gastroenterology, Tokyo Women''s Medical University, Tokyo, Japan;8. Department of Hematology, Tokyo Women''s Medical University, Tokyo, Japan;1. Hospital of LMU Munich, Division of General, Visceral, Vascular and Transplant Surgery, Munich, Bavaria, Germany;2. Hospital of LMU Munich, Division of Nephrology, Department of Medicine IV, Munich, Bavaria, Germany;3. University Hospital Cologne, Department for General, Visceral, Cancer and Transplant Surgery, Cologne, North Rhine-Westphalia, Germany;1. The First People''s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China;2. Department of General Surgery, Wujin Affiliated Hospital of Jiangsu University and The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China;3. Department of Gastrointestinal Sugery, The First People''s Hospital of Changzhou, The Third Affiliated Hospital of Soohow University, Changzhou, Jiangsu, China;1. Department of General, Visceral, and Transplant Surgery, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;2. Walter-Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany;3. Institute of Laboratory Medicine, LMU University Hospitals, Ludwig-Maximilians-Universität Munich, Marchioninistraße 15, 81377 Munich, Germany |
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| Abstract: | BackgroundOsteoarthritis (OA) was a chronic degenerative joint disease. The dysregulation of circular RNAs (circRNAs) has been identified in OA progression. However, the function and regulation mechanism of circ_0114876 in OA remains largely unknown.MethodFirstly, we used LPS-treated C28/I2 cells as a cellular model of OA. Quantificational real-time polymerase chain reaction (qRT-PCR) was used to determine the expression levels of circ_0114876, miRNA-1227-3p, and ADAM10 in OA chondrocytes. Cell Counting Kit-8 (CCK8), 5-ethynyl-20-deoxyuridine (EdU) incorporation assays, flow cytometry, Enzyme-linked immunosorbent assay (ELISA) kit, and western blot were applied to confirm cell proliferation, apoptosis, inflammation, and extracellular matrix.of circ_0114876 in vitro. The interaction between circ_0114876 and its downstream target (miR-1227-3p) and mRNA target ADAM metallopeptidase domain 10 (ADAM10), was evaluated by luciferase assay and RNA immunoprecipitation (RIP) assay.ResultCirc_0114876 and ADAM10 were upregulated and miR-1227-3p was decreased in OA tissues and LPS-treated chondrocytes. Low expression of circ_0114876 promoted proliferation and inhibited apoptosis, inflammation, and extracellular matrix of the LPS-treated chondrocytes. Mechanistically, circ_0114876 functioned in human chondrocytes through targeting miR-1227-3p and ADAM10. Furthermore, miRNA-1227-3p inhibitor reversed the effect of circ_0114876 knockdown on the OA chondrocytes, and ADAM10 overexpression reversed the effect of miR-1227-3p mimic on the OA chondrocytes.ConclusionCirc_0114876 was increased in OA tissues and cells. Circ_0114876 facilitated the progression in the LPS-induced OA cell model via regulating the miR-1227-3p/ADAM10 axis. This study would provide a potentially effective therapeutic strategy for OA progression. |
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