ArticleGene therapy2013
Combination gene therapy targeting on interleukin-1β and RANKL for wear debris-induced aseptic loosening.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Arthrotomy-based preclinical models of particle-induced osteolysis: A systematic review.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017Pooled it
- Genetic applications in arthroplasty: A review.Bulletin of the Hospital for Joint Disease (2013) · 2025Review
- Circular RNA CircSLC8A1 contributes to osteogenic differentiation in hBMSCs via CircSLC8A1/miR-144-3p/RUNX1 in periprosthetic osteolysis.Journal of cellular and molecular medicine · 2023Article
- Particulate and ion forms of cobalt-chromium challenged preosteoblasts promote osteoclastogenesis and osteolysis in a murine model of prosthesis failure.Journal of biomedical materials research. Part A · 2019Article
- Strontium ranelate inhibits wear particle-induced aseptic loosening in mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Article
- Mechanism and Prevention of Titanium Particle-Induced Inflammation and Osteolysis.Frontiers in immunology · 2018Article
- Lentivirus-mediated short hairpin RNA interference targeting TNF-alpha in macrophages inhibits particle-induced inflammation and osteolysis in vitro and in vivo.BMC musculoskeletal disorders · 2016Article
- Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats.Gene therapy · 2015Article
- ER Stress Mediates TiAl6V4 Particle-Induced Peri-Implant Osteolysis by Promoting RANKL Expression in Fibroblasts.PloS one · 2015Article
- Direct interrogation of DNA content distribution in nanoparticles by a novel microfluidics-based single-particle analysis.Nano letters · 2014Article
- Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement.Journal of the Royal Society, Interface · 2014Review
- Pharmacologic augmentation of implant fixation in osteopenic bone.Current osteoporosis reports · 2014Review
- Titanium particle-challenged osteoblasts promote osteoclastogenesis and osteolysis in a murine model of periprosthestic osteolysis.Acta biomaterialia · 2013Article
- Local gene transfer of OPG prevents joint damage and disease progression in collagen-induced arthritis.TheScientificWorldJournal · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
This study investigated the efficacy of a combination gene therapy to repress interleukin-1 (IL-1) and receptor activator of nuclear factor NF-kappa B ligand (RANKL) for the treatment of particulate debris-induced aseptic loosening, and tried to explore the molecular mechanism of the exogenous gene modifications on osteoclastogenesis. RAW cells activated by titanium particles were transduced with DFG-IL-1Ra (retroviral vector encoding IL-1 receptor antagonist) and AAV-OPG (adeno-associated viral vectors-osteoprotegerin) individually or in combination for 4 weeks. Pro-inflammatory cytokines in culture media were determined by enzyme-linked immunosorbent assay, and gene expressions of RANK, IL-1β, c-Fos, TRAF6, JNK1 and CPK were examined using real-time PCR. An established knee-implant-failure mouse model was employed to evaluate the efficacy of the in vivo double-gene therapy. The surgical implantation of a titanium alloy pin into the proximal tibia was followed by monthly challenge with titanium debris. Peri-implant gene transfers of IL-1Ra and OPG (respectively or in combination) were given 3 weeks after surgery. The combination of OPG and IL-1Ra gene transfer exhibited strong synergetic effects in blockage of inflammation and osteoclastogenesis at 8 weeks after gene modification. The combination therapy reversed peri-implant bone resorption and restored implant stability when compared with either single gene transduction. Real-time PCR data indicated that the action of IL-1Ra gene therapy may be mediated via the JNK1 pathway, while the reduction of osteoclastogenesis by OPG gene modification may be regulated by c-Fos expression. In addition, both gene modifications resulted in significant diminishment of TRAF6 expression.
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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.