Exp Mol Med.  2010 Oct;42(10):684-695. 10.3858/emm.2010.42.10.067.

Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits

• Chen B
• Qin J
• Wang H
• Magdalou J
• Chen L

• KMID: 964663
• DOI: http://doi.org/10.3858/emm.2010.42.10.067

Abstract

The study investigated the effects of adenovirus-mediated gene transfection of basic fibroblast growth factor (bFGF), bFGF combined with interleukin-1 receptor antagonist protein (IL-Ra) and/or insulin-like growth factor-1 (IGF-1) both in human osteoarthritis (OA) chondrocytes and rabbits OA model. Human OA chondrocytes were delivered by adenovirus-mediated bFGF, IL-Ra and IGF-1 vectors, respectively. Chondrocyte proliferation, glycosaminoglycan (GAG) content, expression of type II collagen, ADAMTS-5, MMP-13, MMP-3 and TIMP-1 were determined. Rabbit OA model was induced by anterior cruciate ligament transaction (ACLT) in knees. Adenoviral vectors encoding human bFGF, IL-Ra and IGF-1 were injected intraarticularly into the knee joints after ACLT. The effects of adenovirus- mediated gene transfection on rabbit OA were evaluated. In vitro, the transfected genes were expressed in cell supernatant of human OA chondrocytes. AdbFGF group significantly promoted chondrocyte proliferation, and increased GAG and type II collagen synthesis than in the OA group. As two or three genes were transfected in different combinations, there was significant enhancement on the GAG content, type II collagen synthesis, and TIMP-1 levels, while ADAMTS-5, MMP-13, and MMP-3 levels were reduced. In vivo, the transfected genes were expressed in synovial fluid of rabbits. Intraarticular delivery of bFGF enhanced the expression of type II collagen in cartilage and decreased cartilage Mankin score compared with the OA control group (P = 0.047; P < 0.01, respectively). Multiple-gene transfection in different combinations showed better results than bFGF transfection alone. This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA.

Keyword

chondrocytes; fibroblast growth factor 2; gene therapy; insulin-like growth factor I; interleukin-1 receptor antagonist protein; osteoarthritis; transduction, genetic

MeSH Terms

Adenoviridae/*genetics
Animals
Chondrocytes/drug effects/*metabolism
Collagen Type II/genetics/metabolism
Fibroblast Growth Factor 2/*genetics
Gene Therapy/methods
Genetic Vectors/administration & dosage/*genetics
Humans
Insulin-Like Growth Factor I/*genetics/metabolism
Interleukin 1 Receptor Antagonist Protein/*genetics/metabolism
Interleukin-1/genetics/metabolism
Matrix Metalloproteinase 13/genetics/metabolism
Matrix Metalloproteinase 3/genetics/metabolism
Osteoarthritis/*therapy
Rabbits
Tissue Inhibitor of Metalloproteinase-1/genetics
Transfection