Abstract
Summary Statement
Intra-articular injection of humanised monoclonal anti-VEGF antibody (Bevacizumab, Avastin®) in a osteoarthritis rabbit model is related to positive restorative effects in terms of histopathologic evaluation.
Introduction
Vascular endothelial growth factor (VEGF) is generally undetectable in adult human articular cartilage under physiological conditions. Upon exposure to pathological stimulation such as inflammation, hypoxia or accumulating mechanical stress, VEGF would be up regulated in hypertrophic chondrocytes of arthritic cartilage leading to osteophyte formation, disregulation of chondrocyte apoptosis and induction of catabolic factors, including matrix metalloproteinases (MMPs). This in vivo study aims to investigate the potential role of VEGF inhibition to treat Osteoarthritis (OA), through intra-articular injection of Bevacizumab, a humanised monoclonal anti-VEGF antibody, in a OA rabbit model.
Methods
OA was induced in twelve adult male New Zealand rabbits surgically by monolateral Anterior Cruciate Ligament Transection (ACLT). The rabbits were randomly divided into two equal groups (experimental and control). Intra-articular injections of Bevacizumab or saline (control) were given 4 weeks after ACLT and were administered once a week for 4 time. Animal were sacrificed at 2 and 3 month time point an knee analyzed histologically and grossly. Histopathological variables such as the number of fibroblasts and inflammatory cells, collagenous matrix deposition, synovial hyperplasia, granulation tissue formation, vascular proliferation were evaluated.
Results:The macroscopic evaluation of the knee in the experimental group revealed smooth joint surfaces of articular cartilage and no osteophyte formation compared to the control group that showed marked arthritis including synovial hypertrophy and osteophyte formation. Histologic assessment demonstrated, in the experimental group, significantly higher scores concerning number of microvessels, synovial hyperplasia, macrophage infiltration, collagenous matrix deposition, chondrocytes proliferation and apoptosis compared to the control group.
Conclusion
In conclusion, VEGF modulation via intra-articular injection of Bevacizumab in a rabbit model of knee OA, resulted in reduction of articular cartilage degeneration through setting up an appropriate environment that prevent chondrocyte hypertrophy, apoptosis and osteophytes formation by blocking the intrinsic VEGF catabolic pathway, endochondral ossification, and the extrinsic VEGF-induced vascular invasion. VEGF-signaling inhibtion through Bevacizumab represent a potential way to treat OA.
