ArticleJournal of bone and mineral metabolism2022
Regulation of circADAMTS6-miR-324-5p-PIK3R3 ceRNA pathway may be a novel mechanism of IL-1β-induced osteoarthritic chondrocytes.
Article in Journal of bone and mineral metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Review
- Circ72688 Drives Breast Cancer Invasion and Metastasis via the miR-654-5p/ORAI2 Axis.Oncology research · 2026Article
- Exosomal circ-PTPN22 and circ-ADAMTS6 mark T cell exhaustion and neutrophil extracellular traps in Asian intrahepatic cholangiocarcinoma.Molecular therapy. Nucleic acids · 2023Article
- CircRNAs in osteoarthritis: research status and prospect.Frontiers in genetics · 2023Review
- The circRNA circADAMTS6 promotes progression of ESCC and correlates with prognosis.Scientific reports · 2022Article
- Cartilage Homeostasis and Osteoarthritis.International journal of molecular sciences · 2022Review
- ADAMTS6: Emerging roles in cardiovascular, musculoskeletal and cancer biology.Frontiers in molecular biosciences · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionA disintegrin and metallopeptidase with thrombospondin type 1 motif 6 (ADAMTS6)-derived circular RNA (circADAMTS6; hsa_circ_0008667) is a novel regulator in interleukin (IL)-1β-induced apoptosis of human chondrocytes (HCs). Here, we planned to probe into its role and mechanism underlying HCs injury in osteoarthritis. MATERIALS AND
methodsReal time-quantitative PCR and immunoblotting estimated the abundance of RNA and protein, respectively. Cell proliferation and apoptosis were measured by WST-8, EdU, fluorescein isothiocyanate, and caspase3/7 activity assays. Levels of inflammatory cytokines (IL-6 and tumor necrosis factor-α), apoptosis-related proteins (Bcl-2 and Bcl-2-associated X protein), extracellular matrix (ECM)-related proteins (matrix metalloproteinase-13 and collagen type II alpha-1), and PI3K/AKT/mTOR signaling pathway-related proteins (AKT, mTOR, phosphorylated-AKT, and phosphorylated-mTOR) were evaluated by enzyme-linked immunosorbent assays and immunoblotting. Target relationship was confirmed by dual-luciferase reporter, Argonaute-2 immunoprecipitation and RNA pull-down assays.
resultsAbundances of circADAMTS6 and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) were underexpressed, and microRNA (miR)-324-5p was elevated in human osteoarthritic tissues and IL-1β-induced HCs. Overexpressing circADAMTS6 and inhibiting miR-324-5p enhanced proliferation and ECM synthesis, but suppressed apoptosis and inflammatory response in IL-1β-challenged HCs. Besides, silencing circADAMTS6 caused similar effects of IL-1β stress on HCs. Mechanically, there was a direct interaction between miR-324-5p and circADAMTS6 or PIK3R3, and IL-1β-induced activation of PI3K/AKT/mTOR signaling pathway was suppressed by circADAMTS6 overexpression and miR-324-5p silencing. Furthermore, counteractive effects of miR-324-5p upregulation on circADAMTS6 overexpression and PIK3R3 knockdown on miR-324-5p silencing were observed.
conclusionCircADAMTS6-miR-324-5p-PIK3R3 axis might participate in IL-1β-induced HCs dysfunction via competing endogenous RNA mechanism and the PI3K/AKT/mTOR signaling pathway.
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