Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits.
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.
Chen
Biao
B
Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
Qin
Jun
J
Wang
Hui
H
Magdalou
Jacques
J
Chen
Liaobin
L
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000628:therapy*; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014162:Transfection
D024043:Collagen Type II; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3