Abstract
Cartilage neoangiogenesis holds a key role in the development of osteoarthritis (OA) by promoting cartilage degradation with proteoglycan loss, subchondral bone sclerosis, osteophyte formation and synovial hyperplasia. This study aimed to assess the in vivo efficacy of bevacizumab, an antibody against vascular endothelial growth factor (VEGF) in an OA animal model.
24 New Zealand white rabbits underwent anterior cruciate ligament transection in order to spontaneously develop knee OA. Animals were divided into four groups: one receiving a sham intraarticular knee injection (saline) and three groups treated with 5, 10, and 20 mg intraarticular bevacizumab injections. The biological effect of the antibody on cartilage and synovium was evaluated through histology and quantified with the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemical analysis was conducted to investigate type 2 collagen, aggrecan, and matrix metalloproteinase 13 (MMP-13) expression in both cartilage and synovium.
Intraarticular bevacizumab led to a significant reduction of cartilage degeneration and synovial OA alterations. Immunohistochemistry showed a significantly reduced MMP-13 expression in all experimental groups, with the one receiving 20 mg bevacizumab showing the lowest. Furthermore, the antibody showed to increment the production of aggrecan and type 2 collagen after administration of 5, 10, and 20 mg. The group treated with 20 mg showed the highest levels of type 2 collagen expression, while aggrecan content was even higher than in the healthy cartilage.
Intraarticular bevacizumab has demonstrated to effectively arrest OA progression in our model, with 20 mg being the most efficacious dose. By inhibiting cartilage and synovial neoangiogenesis, bevacizumab may serve as a possible disease-modifying osteoarthritis drug (DMOAD) in the next future.
