ArticleAnnals of the rheumatic diseases2020
TGFβ attenuates cartilage extracellular matrix degradation via enhancing FBXO6-mediated MMP14 ubiquitination.
Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions.Journal of translational medicine · 2024Pooled it
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- Single-cell and spatial transcriptomics analysis of osteoarthritis: pathway regulation, cell interaction networks, and therapeutic translation.Journal of translational medicine · 2026Review
- Targeting E3 Ubiquitin Ligases in Post-Traumatic Osteoarthritis: Therapeutic Opportunities and Pharmacological Perspectives.Pharmaceutics · 2026Review
- Melatonin Exerts Chondroprotective Effects Against Osteoarthritis by Promoting PI3K/AKT/FoxO3-Mediated Mitophagy.The Kaohsiung journal of medical sciences · 2026Article
- Network Analysis Identifies Microsomal Glutathione S-Transferase as a Potential Regulator of Oxidative Stress and Proteasome Dysfunction in Human Osteoarthritic Menisci.FASEB bioAdvances · 2026Article
- CAP-CD56Bioactive materials · 2026Article
- FBXO6 mediated ubiquitination of SLC3A2 drives ferroptosis in ulcerative colitis: a machine learning and SHAP discovery.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Circular RNA circPLXNC1 functions as an inhibitor of senescence by regulating autophagy in osteoarthritis.International journal of biological sciences · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- RNF152-mediated, ubiquitin-dependent degradation of HSP27 activates the PI3K/AKT pathway, driving synovial inflammatory cascades in TMJOA.Arthritis research & therapy · 2025Article
- HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes.Inflammation · 2025Article
- Upregulation of ACSL1 in synovial macrophages promotes lipid peroxidation via the IκB/NF-κB pathway to accelerate osteoarthritis.Journal of orthopaedic translation · 2025Article
- PRP and hypertonic glucose injections improve outcomes in patients with early- to middle-stage knee osteoarthritis: a multicenter retrospective study.BMC musculoskeletal disorders · 2025Article
- Y-box binding protein 1 stabilizes EP300 mRNA and promotes forkhead box C1 H3K27Ac to aggravate chondrocyte injury in osteoarthritis.Journal of cell communication and signaling · 2025Article
- RO5126766 attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through mediating the ERK pathway.Journal of orthopaedic translation · 2025Article
- LncRNA ENST00000581911 Regulates Extraocular Muscle Remodeling by Interacting With KHSRP in Thyroid Eye Disease.Investigative ophthalmology & visual science · 2025Article
- The multifaceted roles of E3 ubiquitin ligases in osteoarthritis.Frontiers in cell and developmental biology · 2025Review
- Identification of WDR74 and TNFRSF12A as biomarkers for early osteoarthritis using machine learning and immunohistochemistry.Frontiers in immunology · 2025Article
- Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system.Materials today. Bio · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesFBXO6, a component of the ubiquitin E3 ligases, has been shown to bind high mannose N-linked glycoproteins and act as ubiquitin ligase subunits. Most proteins in the secretory pathway, such as matrix metalloproteinases, are modified with N-glycans and play important roles in the development of osteoarthritis (OA). However, whether FBXO6 exerts regulatory effects on the pathogenesis of OA remains undefined.
methodsThe expression of FBXO6 was examined in the cartilage of human and multiple mouse OA models. The role of FBXO6 in cartilage degeneration was analysed with
resultsThe expression of FBXO6 decreased in the cartilage from human OA samples, anterior cruciate ligament transaction (ACLT) -induced OA samples, spontaneous OA STR/ort samples and aged mice samples. Global knockout or conditional knockout of FBXO6 in cartilage promoted experimental OA process. The molecular mechanism study revealed that FBXO6 decreased MMP14 by ubiquitination and degradation, leading to inhibited proteolytic activation of MMP13. Interestingly, FBXO6 expression is regulated by transforming growth factor β (TGFβ)-SMAD2/3 signalling pathway. Therefore, the overexpression of FBXO6 protected mice from post-injury OA development.
conclusionsTGFβ-SMAD2/3 signalling pathway suppressed MMP13 activation by upregulating of FBXO6 transcription and consequently promoting MMP14 proteasomal degradation. Inducement of FBXO6 expression in OA cartilage might provide a promising OA therapeutic strategy.
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