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IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.
Abstract: Repair of cartilage defects involves sequential participation of specific hormones and growth factors with potential impairment by inflammatory cytokines. We explored an in vivo gene therapy treatment to supply adenoviral vectors carrying the genes of interleukin-1 receptor antagonist protein (IL-1ra) and insulinlike growth factor-1 (IGF-1), hoping to enhance repair of full-thickness equine chondral defects treated with microfracture. We asked whether our treatment could (1) increase proteoglycan and Type II collagen content in the repair tissue, (2) improve the macroscopic and histomorphometric aspect of the repair tissue, and (3) induce prolonged and increased IL-1ra and IGF-1 production in treated joints. Twelve horses had full-thickness chondral defects created in their carpus and stifle followed by microfracture. Joints were injected with either equine IL-1ra/IGF-1 adenoviral preparation or Gey's balanced salt solution. Sixteen weeks later, defect healing was evaluated macroscopically, histologically, histochemically, and biochemically. Production of IL-1ra and IGF-1 was measured by enzyme-linked immunosorbent assay and radioimmunoassay. We found increased proteoglycan content in treated defects along with augmented Type II collagen associated with substantial transgene expression of IL-1ra during the first 3 weeks. These data suggest in vivo gene therapy can improve biologic processes associated with chondral defect repair.
Publication Date: 2007-05-31 PubMed ID: 17534189DOI: 10.1097/BLO.0b013e3180dca05fGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper investigates gene therapy as a method for improving the repair process of cartilage defects in horses. The researchers specifically tested the use of two genes, interleukin-1 receptor antagonist protein (IL-1ra) and insulinlike growth factor-1 (IGF-1), to foster better repair and recovery.
Research Background
- The study aims to advance the understanding of cartilage defects repair which involves hormones, growth factors, and potentially harmful inflammatory cytokines.
- The scientists tested in vivo gene therapy to supply adenoviral vectors or gene carriers, which contain genes for IL-1ra and IGF-1.
- These genes were selected because potential benefits include increased proteoglycan and Type II collagen content in the repair tissue; improved macroscopic and histomorphometric properties; prolonged activated IL-1ra and IGF-1 production in treated joints.
Research Methodology
- Full-thickness chondral defects were created in the joins of twelve horses, and microfracture was applied as a treatment model.
- The joints were injected with either the adenoviral preparation delivering equine IL-1ra/IGF-1 gene therapy, or Gey’s balanced salt solution as a control.
- After 16 weeks, healing was evaluated macroscopically (visible changes), histologically (tissue structure), histochemically (chemical changes in tissue), and biochemically (molecular composition).
- Production of IL-1ra and IGF-1 was detected and measured through enzyme-linked immunosorbent assay and radioimmunoassay.
Results and Conclusions
- The findings reveal increased proteoglycan content in the defects treated with gene therapy. Proteoglycans are vital for the structure and function of cartilage, indicating positive repair progression.
- The therapy also led to an increase in Type II collagen, which is crucial for cartilage strength and resistance.
- A notable increase in the expression of IL-1ra was observed during the first 3 weeks following therapy. However, the study does not provide data on IGF-1 expression.
- The results imply that in vivo gene therapy, delivering IL-1ra and potentially IGF-1, can enhance the biologic processes associated with cartilage defect repair.
Cite This Article
APA
Morisset S, Frisbie DD, Robbins PD, Nixon AJ, McIlwraith CW.
(2007).
IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.
Clin Orthop Relat Res, 462, 221-228.
https://doi.org/10.1097/BLO.0b013e3180dca05f Publication
Researcher Affiliations
- Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80524, USA.
MeSH Terms
- Animals
- Carpus, Animal / injuries
- Carpus, Animal / pathology
- Carpus, Animal / surgery
- Cartilage, Articular / injuries
- Cartilage, Articular / metabolism
- Cartilage, Articular / pathology
- Chondrocytes / metabolism
- Chondrocytes / pathology
- Chondrogenesis / genetics
- Collagen Type II / metabolism
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Femoral Fractures / pathology
- Femoral Fractures / physiopathology
- Femoral Fractures / surgery
- Gene Expression
- Genetic Therapy / methods
- Genetic Vectors
- Hindlimb
- Horses
- Insulin-Like Growth Factor I / genetics
- Interleukin 1 Receptor Antagonist Protein / genetics
- Proteoglycans / metabolism
- Stifle / injuries
- Stifle / pathology
- Stifle / surgery
- Up-Regulation
- Wound Healing
Citations
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