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

Biao Chen,Jacques Magdalou,Liaobin Chen,Hui Wang,Jun Qin

doi: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.

Highlights

Osteoarthritis (OA) is a degenerative joint disease, which charactered by destruction of articular cartilage, remodeling of the subchondral bone, joint marginal osteophyte formation and synovitis
This study shows that introduction of basic fibroblast growth factor (bFGF) by transfection has a protective effect both on cultured human OA chondrocytes and on cartilage degradation in rabbit OA model
The in vitro results revealed that bFGF promoted chondrocyte proliferation in OA, and enhanced GAG and type II collagen synthesis

Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disease, which charactered by destruction of articular cartilage, remodeling of the subchondral bone, joint marginal osteophyte formation and synovitis It is responsible for joint pain in middle-aged and older people and seriously influences their quality of life (De Ceuninck, 2007). Advanced OA can only be managed by surgical replacement of joints, but there remain problems regarding the degree of invasion, cost and long-term prognosis (Berenbaum, 2008). For these reasons, an im proved method that inhibits OA progression is needed. It offers a radically new approach for treating OA (Evans et al, 2004)

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