ArticleAnnals of the rheumatic diseases2015
Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling.
Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 154 citations in OpenAlex.
- Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial.The Journal of international medical research · 2018Trial
- Adipose-Joint Crosstalk in Obesity-Induced Osteoarthritis: Mechanisms, Biomarkers, and Translational Therapeutic Opportunities.Current rheumatology reports · 2026Review
- Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells.Science immunology · 2026Article
- Advances in the pathology and treatment of osteoarthritis.Journal of advanced research · 2025Review
- Single-cell sequencing reveals a senescent immune landscape in bone marrow lesions inducing articular cartilage damage in osteoarthritis.Bone research · 2025Article
- Starlike Au nanoparticle unleashing siDDIT3 and photothermal power to combat ferroptosis - driven osteoarthritis.Journal of nanobiotechnology · 2025Article
- Analysis of progranulin concentration in corneal epithelium and tears as a possible biomarker in the clinical diagnosis and progression of keratoconus.International ophthalmology · 2025Article
- Electroacupuncture delays the progression of juvenile collagen-induced arthritis via regulation NLRP3/ NF-κB signaling pathway -mediated pyroptosis and its influence on autophagy.Clinical rheumatology · 2025Article
- SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch.Bone research · 2025Article
- Progranulin derivative attenuates lung neutrophilic infiltration from diesel exhaust particle exposure.Allergy · 2025Article
- NLRP3 overexpression exacerbated synovium tissue degeneration in juvenile collagen-induced arthritis.Scientific reports · 2025Article
- Metabolism-Related Adipokines and Metabolic Diseases: Their Role in Osteoarthritis.Journal of inflammation research · 2025Review
- Thrombospondin-1 mitigates osteoarthritis progression by inhibiting mechanical stress-induced chondrocyte ferroptosis via the integrin/YAP pathway.Frontiers in immunology · 2025Article
- Molecular mechanisms and targeted therapy of progranulin in metabolic diseases.Frontiers in endocrinology · 2025Review
- Cellular and molecular mechanisms underlying obesity in degenerative spine and joint diseases.Bone research · 2024Review
- Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson's Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice.Molecular neurobiology · 2024Article
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects.BMC musculoskeletal disorders · 2024Article
- Obesity, Metabolic Syndrome, and Osteoarthritis Require Integrative Understanding and Management.Biomedicines · 2024Review
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveProgranulin (PGRN) was previously isolated as an osteoarthritis (OA)-associated growth factor. Additionally, PGRN was found to play a therapeutic role in inflammatory arthritis mice models through antagonising tumour necrosis factor α (TNF-α). This study was aimed at investigating the role of PGRN in degradation of cartilage and progression of OA.
methodsProgression of OA was analysed in both spontaneous and surgically induced OA models in wild type and PGRN-deficient mice. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry and ELISA. Additionally, mRNA expression of degenerative factors and catabolic markers known to be involved in cartilage degeneration in OA were analysed. Furthermore, the anabolic effects and underlying mechanisms of PGRN were investigated by in vitro experiments with primary chondrocytes.
resultsHere, we found that deficiency of PGRN led to spontaneous OA-like phenotype in 'aged' mice. Additionally, PGRN-deficient mice exhibited exaggerated breakdown of cartilage structure and OA progression, while local delivery of recombinant PGRN protein attenuated degradation of cartilage matrix and protected against OA development in surgically induced OA models. Furthermore, PGRN activated extracellular signal-regulated kinases (ERK) 1/2 signalling and elevated the levels of anabolic biomarkers in human chondrocyte, and the protective function of PGRN was mediated mainly through TNF receptor 2. Additionally, PGRN suppressed inflammatory action of TNF-α and inhibited the activation of β-Catenin signalling in cartilage and chondrocytes.
conclusionsCollectively, this study provides new insight into the pathogenesis of OA, and also presents PGRN as a potential target for the treatment of joint degenerative diseases, including 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 OpenQuestion graph.