ArticleAnnals of the rheumatic diseases2021
14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis.
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 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- Single-Cell Transcriptomic Profiling Reveals Superficial Zone Chondrocytes as a Catabolic and Senescent Focus in Osteoarthritis Cartilage.Cartilage · 2026Article
- Regulation of microglial activation by progranulin through the NF-κB pathway in subarachnoid hemorrhage and its effect on white matter injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- Senescent Synovial Intimal Fibroblasts Aggravate Osteoarthritis by Regulating Macrophage Polarization and Chondrocyte Phenotype Through ANGPTL4-α5β1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated single-cell and experimental validation links effector chondrocyte-associated oxidative stress to EIF6-related p47phox-NOX2 signaling in osteoarthritis.Frontiers in physiology · 2026Article
- CORO1A links inflammatory chondrocyte subpopulations to immune microenvironment alterations in osteoarthritis: an integrative multi-omics and single-cell study.Frontiers in immunology · 2026Article
- Eugenol preserves chondrocyte extracellular matrix homeostasis by modulating the ALK1/ALK5-associated TGF-β/Smad signaling axis.Frontiers in pharmacology · 2026Article
- Fat modifications protect joints from degrading.Nature aging · 2025Article
- ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis.Nature aging · 2025Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Cytosolic phospholipase A2 as a therapeutic target for degenerative joint diseases.Bone research · 2025Article
- Multiomics Comparison of Proline-Rich Peptide-Enhanced Hyaluronic Acid Gels Versus Conventional Regenerative Materials: An Early Wound-Healing Model.Journal of periodontal research · 2025Article
- Extracellular Vesicles From Schistosoma mansoni Adult Worms Stimulate IL-10 Release by B Cells.Parasite immunology · 2025Article
- A multi-tissue human knee single-cell atlas identifies that osteoarthritis reduces regenerative tissue stem cells while increasing inflammatory pain macrophages.Communications biology · 2025Article
- GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis.Journal of advanced research · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Multi-omics integration reveals YWHAE as a key mediator of ferroptosis in ARDS.Functional & integrative genomics · 2025Article
- From metabolomics to therapeutics: identifying causal metabolites and potential drugs for the treatment of osteoarthritis.Inflammopharmacology · 2025Article
- Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway.Journal of cellular and molecular medicine · 2025Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.Cell genomics · 2025Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesOsteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA.
methodsBiochemical copurification and proteomics screen were performed to isolate the intracellular cofactors of TNFR2 complex. Bulk and single cell RNA-seq were employed to determine 14-3-3 epsilon (14-3-3ε) expression in human normal and OA cartilage. Transcription factor activity screen was used to isolate the transcription factors downstream of TNFR2/14-3-3ε. Various cell-based assays and genetically modified mice with naturally occurring and surgically induced OA were performed to examine the importance of this pathway in chondrocytes and OA.
resultsSignalling molecule 14-3-3ε was identified as an intracellular component of TNFR2 complexes in chondrocytes in response to progranulin (PGRN), a growth factor known to protect against OA primarily through activating TNFR2. 14-3-3ε was downregulated in OA and its deficiency deteriorated OA. 14-3-3ε was required for PGRN regulation of chondrocyte metabolism. In addition, both global and chondrocyte-specific deletion of 14-3-3ε largely abolished PGRN's therapeutic effects against OA. Furthermore, PGRN/TNFR2/14-3-3ε signalled through activating extracellular signal-regulated kinase (ERK)-dependent Elk-1 while suppressing nuclear factor kappa B (NF-κB) in chondrocytes.
conclusionsThis study identifies 14-3-3ε as an inducible component of TNFR2 receptor complex in response to PGRN in chondrocytes and presents a previously unrecognised TNFR2 pathway in the pathogenesis of OA.
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