Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

Abstract

IntroductionAngiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection.MethodsFirst, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group).ResultsHistologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group.ConclusionsConsidering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0427-y) contains supplementary material, which is available to authorized users.

Inflammation in joint injury and post-traumatic osteoarthritis

“…In cartilage, ADAMTS-4 levels did not change while MMP-13 was downregulated. These results are consistent with ACL-transection models in rabbits and rats [46] [47] [48], rodent meniscectomy [30, 49] models, and observations in canine cranial cruciate ligament tears [27]. Thus, non-cartilaginous soft tissues may be important sources of inflammatory molecules and proteases that contribute to cartilage matrix catabolism early after injury.…”

Emerging targets in osteoarthritis therapy

“…Gene expression profiling identified STC1, a gene encoding stanniocalcin-1, which regulates angiogenic sprouting via the VEGF/VEGF receptor 2 pathway, as the most highly up-regulated gene in inflamed synovial membrane compared to non-inflamed synovium from the same OA patients [123]. A recent study shows that VEGF blockade with bevacizumab inhibits post-traumatic OA in a rabbit model with pain relief possibly associated with prevention of both synovitis and angiogenesis [124]. …”

Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

“…Injection of VEGF into animal joints induces OA and VEGF stimulates degeneration of articular chondrocytes 6 . Anti-VEGF therapy is therefore emerging as a potential OA treatment 7 .…”