ArticleHuman gene therapy2019
Combinatorial Prg4 and Il-1ra Gene Therapy Protects Against Hyperalgesia and Cartilage Degeneration in Post-Traumatic Osteoarthritis.
Article in Human gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Lubricin in experimental and naturally occurring osteoarthritis: a systematic review.Osteoarthritis and cartilage · 2020Pooled it
- Serum Dkk-1 Is Associated with Pain Intensity, Flare-Ups, and Bone Mineral Density in Non-Obese Patients with Knee Osteoarthritis: A Single-Center, Cross-Sectional Study.International journal of molecular sciences · 2026Article
- What's next for osteoarthritis gene therapy?Frontiers in bioengineering and biotechnology · 2026Review
- The inflammatory microenvironment repurposes BMP-2 signaling to drive pathological osteophyte formation in osteoarthritis.Frontiers in immunology · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and promotes cartilage repair in surgically induced osteoarthritis animal models.Gene therapy · 2025Article
- Review
- The Intra-Articular Delivery of a Low-Dose Adeno-Associated Virus-IL-1 Receptor Antagonist Vector Alleviates the Progress of Arthritis in an Osteoarthritis Rat Model.Pharmaceutics · 2024Article
- Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review.Croatian medical journal · 2024Review
- Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management-A Narrative Review.Journal of personalized medicine · 2024Review
- Targeting CD44 Receptor Pathways in Degenerative Joint Diseases: Involvement of Proteoglycan-4 (PRG4).Pharmaceuticals (Basel, Switzerland) · 2023Review
- An Integrated View of Stressors as Causative Agents in OA Pathogenesis.Biomolecules · 2023Review
- Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.Frontiers in medicine · 2023Article
- Biomaterial-Based Gene Delivery: Advanced Tools for Enhanced Cartilage Regeneration.Drug design, development and therapy · 2023Review
- Intra-Articular Adeno-Associated Virus-Mediated Proteoglycan 4 Gene Therapy for Preventing Posttraumatic Osteoarthritis.Human gene therapy · 2022Article
- Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property Facilitates/promotes growth plate injury repair.Bioactive materials · 2022Article
- Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022Review
- Intra-articular Injection of Lornoxicam and MicroRNA-140 Co-loaded Cationic Liposomes Enhanced the Therapeutic Treatment of Experimental Osteoarthritis.AAPS PharmSciTech · 2021Article
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- Tendon and motor phenotypes in theeLife · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Osteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss of articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain and motor impairment. Despite the economic and health impacts, current medical therapies are targeted at symptomatic relief of OA and fail to alter its progression. Given the complexity of OA pathogenesis, we hypothesized that a combinatorial gene therapy approach, designed to inhibit inflammation with interleukin-1 receptor antagonist (IL-1Ra) while promoting chondroprotection using lubricin (PRG4), would improve preservation of the joint compared to monotherapy alone. Employing two surgical techniques to model mild, moderate and severe posttraumatic OA, we found that combined delivery of helper-dependent adenoviruses (HDVs), expressing IL-1Ra and PRG4, preserved articular cartilage better than either monotherapy in both models as demonstrated by preservation of articular cartilage volume and surface area. This improved protection was associated with increased expression of proanabolic and cartilage matrix genes together with decreased expression of catabolic genes and inflammatory mediators. In addition to improvements in joint tissues, this combinatorial gene therapy prolonged protection against thermal hyperalgesia compared to either monotherapy. Taken together, our results show that a combinatorial strategy is superior to monotherapeutic approaches for treatment of posttraumatic OA.
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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.