Detection of vascular endothelial growth factor (VEGF) in moderate osteoarthritis in a rabbit model

Abstract

Vascular endothelial growth factor (VEGF) is detectable in later stages of human osteoarthritis (OA), but not in the healthy articular cartilage. Due to its capacity to increase matrix metalloproteinases and to decrease their inhibitors (tissue inhibitors of metalloproteinases or TIMPs) VEGF seems to play an important role in the development of osteoarthrosis. In late stages of osteoarthritis, invasion of blood vessels from the subchondral growth plate, synovitis with angiogenesis and osteophyte growth is observable. Several studies have revealed a central role for VEGF in all these phenomena. In order to investigate whether VEGF participates in early changes of OA or may even possess characteristics of a marker of OA, we developed an experimental posttraumatic OA New Zealand White rabbit animal model. In four skeletally mature New Zealand White rabbits, OA was induced by joint instability after transsection of the anterior cruciate ligament in both knees. After eight weeks the animals were killed. OA was verified histologically using the Mankin scale. Expression of VEGF was detected by immunohistochemistry and RT-PCR. Proteoglycans were evaluated by using HE and safranin-O staining. Four non-surgically treated animals acted as a control. The mean Mankin score was 5.11 (±2.14), corresponding to a moderate OA. VEGF and VEGF transcripts were detectable in the cartilage of early experimental posttraumatic OA rabbits. Control samples remained negative for VEGF mRNA and protein. The results of this study are promising concerning the role of VEGF as a diagnostic marker. VEGF could further be participated in early changes of OA. A therapeutic approach by modulation of VEGF production could be a possibility for the future.