ArticleMolecular medicine (Cambridge, Mass.)2012
Benefits of recombinant adeno-associated virus (rAAV)-mediated insulinlike growth factor I (IGF-I) overexpression for the long-term reconstruction of human osteoarthritic cartilage by modulation of the IGF-I axis.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- Evaluation of the therapeutic and the chemical effects of balneological treatment on clinical and laboratory parameters in knee osteoarthritis: a randomized, controlled, single-blinded trial.International journal of biometeorology · 2022Trial
- Gene Therapy for the Treatment of Osteoarthritis: Advances and Prospective.Current pharmaceutical design · 2026Review
- Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes to treat osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.Reviews in endocrine & metabolic disorders · 2024Review
- Causal Effects of Plasma Proteome on Osteoporosis and Osteoarthritis.Calcified tissue international · 2023Article
- Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.Frontiers in medicine · 2023Article
- The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity.Military Medical Research · 2022Review
- Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo.Advanced materials (Deerfield Beach, Fla.) · 2021Article
- A New Method to Develop the Primate Model of Knee Osteoarthritis With Focal Cartilage Defect.Frontiers in bioengineering and biotechnology · 2021Article
- Effects of GH/IGF axis on bone and cartilage.Molecular and cellular endocrinology · 2021Review
- Comprehensive evaluation of differential long non-coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra.Experimental and therapeutic medicine · 2020Article
- Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis.BioMed research international · 2020Article
- Effects of rAAV-MediatedJournal of clinical medicine · 2019Article
- Onset and Progression of Human Osteoarthritis-Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?International journal of molecular sciences · 2018Review
- Cross-Coupling Effects of Silencing of Cyclooxygenase-2 (COX-2)/Aggrecanase-1 and Over-Expressed Insulin-Like Growth Factor 1 (IGF-1) in an Osteoarthritis Animal Model.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Peripheral blood aspirates overexpressing IGF-I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes.Journal of cellular and molecular medicine · 2017Article
- Customized biomaterials to augment chondrocyte gene therapy.Acta biomaterialia · 2017Article
- rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model.International journal of nanomedicine · 2017Article
- TGF-β gene transfer and overexpression via rAAV vectors stimulates chondrogenic events in human bone marrow aspirates.Journal of cellular and molecular medicine · 2016Article
- New trends in articular cartilage repair.Journal of experimental orthopaedics · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Administration of therapeutic genes to human osteoarthritic (OA) cartilage is a potential approach to generate effective, durable treatments against this slow, progressive disorder. Here, we tested the ability of recombinant adeno-associated virus (rAAV)-mediated overexpression of human insulinlike growth factor (hIGF)-I to reproduce an original surface in human OA cartilage in light of the pleiotropic activities of the factor. We examined the proliferative, survival and anabolic effects of the rAAV-hIGF-I treatment in primary human normal and OA chondrocytes in vitro and in explant cultures in situ compared with control (reporter) vector delivery. Efficient, prolonged IGF-I secretion via rAAV stimulated the biological activities of OA chondrocytes in all the systems evaluated over extended periods of time, especially in situ, where it allowed for the long-term reconstruction of OA cartilage (at least for 90 d). Remarkably, production of high, stable amounts of IGF-I in OA cartilage using rAAV advantageously modulated the expression of central effectors of the IGF-I axis by downregulating IGF-I inhibitors (IGF binding protein [IGFBP]-3 and IGFBP4) while up-regulating key potentiators (IGFBP5, the IGF-I receptor and downstream mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 [MAPK/ERK-1/2] and phosphatidylinisitol-3/Akt [PI3K/Akt] signal transduction pathways), probably explaining the enhanced responsiveness of OA cartilage to IGF-I treatment. These findings show the benefits of directly providing an IGF-I sequence to articular cartilage via rAAV for the future treatment of human osteoarthritis.
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Registered trials
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