ArticleAnnals of the rheumatic diseases2021
circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1.
Article in Annals of the rheumatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 122 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- YTH N6-methyladenosine RNA binding protein 2 mediated mMolecular biomedicine · 2026Article
- Circular RNA circPLXNC1 functions as an inhibitor of senescence by regulating autophagy in osteoarthritis.International journal of biological sciences · 2026Article
- Molecular mediators of motion: RNA-RBP networks in exercise-induced osteoarthritis protection.Frontiers in genetics · 2026Review
- MSC Membrane-Coated circPROSC-siRNA Nanoparticles for Ameliorating Craniosynostosis by Inhibiting Premature Suture Ossification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025Review
- Molecular Basis of Intron Retention inInternational journal of molecular sciences · 2025Article
- CircTBCK protects against osteoarthritis by regulating extracellular matrix and autophagy.Human cell · 2025Article
- PDE4B promotes JNK/NLRP3 activation in the nucleus pulposus and mediates intervertebral disc degeneration.Scientific reports · 2025Article
- sdRNA-D43 derived from small nucleolar RNA snoRD43 improves chondrocyte senescence and osteoarthritis progression by negatively regulating PINK1/Parkin-mediated mitophagy pathway via dual-targeting NRF1 and WIPI2.Cell communication and signaling : CCS · 2025Article
- Non-coding RNAs in osteoarthritis and osteoporosis-related hip fractures: molecular biomarkers for precision diagnosis and prognosis.Frontiers in endocrinology · 2025Review
- Circular RNAs Binding to RNA-Binding Proteins.Advances in experimental medicine and biology · 2025Review
- CircFndc3b Mediates Exercise-Induced Neuroprotection by Mitigating Microglial/Macrophage Pyroptosis via the ENO1/KLF2 Axis in Stroke Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Midline 1 associated with Fas signaling enhances murine antigen-induced arthritis.Frontiers in cell and developmental biology · 2025Article
- Non-coding RNA in cartilage regeneration: regulatory mechanism and therapeutic strategies.Frontiers in bioengineering and biotechnology · 2025Review
- RNA-binding proteins regulate osteoarthritis via RNA metabolism regulation.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- The circUbqln1, regulated by XBP1s, interplays with 14-3-3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism.Journal of advanced research · 2024Article
- Article
- Superenhancer-driven circRNA Myst4 involves in pulmonary artery smooth muscle cell ferroptosis in pulmonary hypertension.iScience · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCircular RNAs (circRNAs) have emerged as significant biological regulators. Herein, we aimed to elucidate the role of an unidentified circRNA (circPDE4B) that is reportedly downregulated in osteoarthritis (OA) tissues.
methodsThe effects of circPDE4B were explored in human and mouse chondrocytes in vitro. Specifically, RNA pull-down (RPD)-mass spectrometry analysis (MS), immunoprecipitation, glutathione-S-transferase (GST) pull-down, RNA immunoprecipitation and RPD assays were performed to verify the interactions between circPDE4B and the RIC8 guanine nucleotide exchange factor A (RIC8A)/midline 1 (MID1) complex. A mouse model of OA was also employed to confirm the role of circPDE4B in OA pathogenesis in vivo.
resultscircPDE4B regulates chondrocyte cell viability and extracellular matrix metabolism. Mechanistically, FUS RNA binding protein (FUS) was found to promote the splicing of circPDE4B, while downregulation of circPDE4B in OA is partially caused by upstream inhibition of FUS. Moreover, circPDE4B facilitates the association between RIC8A and MID1 by acting as a scaffold to promote RIC8A degradation through proteasomal degradation. Furthermore, ubiquitination of RIC8A at K415 abrogates RIC8A degradation. The circPDE4B-RIC8A axis was observed to play an important role in regulating downstream p38 mitogen-activated protein kinase (MAPK) signalling. Furthermore, delivery of a circPDE4B adeno-associated virus (AAV) abrogates the breakdown of cartilage matrix by medial meniscus destabilisation in mice, whereas a RIC8A AAV induces the opposite effect.
conclusionThis work highlights the function of the circPDE4B-RIC8A axis in OA joints, as well as its regulation of MAPK-p38, suggesting this axis as a potential therapeutic target for OA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.