ArticleArthritis research & therapy2017
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models.
Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Sortilin is Associated with PGRN-Mediated Endoplasmic Reticulum Stress and Activation of Microglia in a Rat Model of Degenerative Cervical Myelopathy.Neuromolecular medicine · 2026Article
- Gut microbial alterations associated with the exacerbation of experimental autoimmune uveitis in PGRN-deficient mice.Frontiers in immunology · 2026Article
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair potential in degenerative conditions.Osteoarthritis and cartilage · 2025Article
- TNFα Receptor 1 and Not Receptor 2 Affect Annulus Fibrosus and Nucleus Pulposus Response to Cytokine Challenge in a Rat Model.JOR spine · 2025Article
- Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway.Journal of cellular and molecular medicine · 2025Article
- Molecular mechanisms and targeted therapy of progranulin in metabolic diseases.Frontiers in endocrinology · 2025Review
- Metabolism-Related Adipokines and Metabolic Diseases: Their Role in Osteoarthritis.Journal of inflammation research · 2025Review
- 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
- Advancing osteoarthritis therapy with GMOCS hydrogel-loaded BMSCs-exos.Journal of nanobiotechnology · 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
- Atsttrin regulates osteoblastogenesis and osteoclastogenesis through the TNFR pathway.Communications biology · 2023Article
- Controlled-Release Hydrogel Microspheres to Deliver Multipotent Stem Cells for Treatment of Knee Osteoarthritis.Bioengineering (Basel, Switzerland) · 2023Article
- Advanced Hydrogel-Based Strategies for Enhanced Bone and Cartilage Regeneration: A Comprehensive Review.Gels (Basel, Switzerland) · 2023Review
- IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.Experimental & molecular medicine · 2023Article
- Injectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing.Biomaterials · 2023Article
- Progranulin regulation of autophagy contributes to its chondroprotective effect in osteoarthritis.Genes & diseases · 2023Article
- Therapeutic potential of TNFR2 agonists: a mechanistic perspective.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAtsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved.
methodsSurgically induced and noninvasive rupture OA models were established in mouse and rat, respectively. Cartilage degradation and OA were evaluated using Safranin O staining, immunohistochemistry, and ELISA. Additionally, expressions of pain-related markers, degenerative factors, and anabolic and catabolic markers known to be involved in OA were analyzed. Furthermore, the anabolic and anti-catabolic effects and underlying mechanisms of Atsttrin were determined using in-vitro assays with primary chondrocytes.
resultsHerein, we found Atsttrin effectively prevented the accelerated OA phenotype associated with PGRN deficiency. Additionally, Atsttrin exhibited a preventative effect in OA by protecting articular cartilage and reducing OA-associated pain in both nonsurgically induced rat and surgically induced murine OA models. Mechanistic studies revealed that Atsttrin stimulated TNFR2-Akt-Erk1/2-dependent chondrocyte anabolism, while inhibiting TNFα/TNFR1-mediated inflammatory catabolism.
conclusionsThese findings not only provide new insights into the role of PGRN and its derived engineered protein Atsttrin in cartilage homeostasis as well as OA in vivo, but may also lead to new therapeutic alternatives for OA as well as other relative degenerative joint diseases.
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Registered trials
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.