VEGF induced osteoarthritis- a new model of osteoarthritis

Objective: Osteoarthritis (OA) is a remarkably common joint disease with limited treatment modalities. Broadening the treatment range requires models accurately mimicking OA pathogenesis. Our study proposes a new model of OA initiated by vascular endothelial growth factor (VEGF). The model is juxtaposed to the known model of collagenase-induced osteoarthritis. Based on the hypothesis that following joint overloading, proliferation of blood vessels and their increased perfusion result in increased intra-articular pressure. When unrestrained, injury to the joint elements is anticipated. Materials and methods: Mice were injected either with a single or repeated dose of 1/20 (ìg/ìl) murine recombinant VEGF165 ,or Collagenase 1/ 20 (mg/ ìl) or Collagenase 1/ 50 (mg/ ìl), all dissolved in ddH2O, into the left knee joints and sacrificed after 1,2,3,4,6 and 8 weeks. Mice injected with saline and sacrificed after 2 and 8 weeks and untreated mice (sham) were used as control. The knee joints were evaluated for known parameters of OA: Macroscopically- change in color, swelling, movement limitation, deformity, exc. Radiographs- flattening, border irregularity, osteophytes, exc. Scintigraphy- increased uptake of 99Tc by injected knees, indicating osteogenesis. Histological evaluation- using histomorphometry. Results: Macroscopically, edema was evident starting first week after VEGF injection. Unlike the collagenase-injected knees, no signs of deformity or movement limitation were detected. Radiographs have shown clear evidence of flattening and irregular borders, starting third week after repeated and single injections of VEGF and Collagenase injection. Scintigraphy had shown increased uptake in the VEGF and Collagenase injected knees. Histological evaluations showed similar findings in both VEGF and collagenase-injected knees, including changes in cartilage, as decreased thickness and chondrocytes amount. Conclusions: Macroscopic, radiographic and histological evaluations and Scintigraphy demonstrated an osteoarthritic like image. VEGF, known to exist in osteoarthritic knees, may have a role in osteoarthritis formation. Therefore, Anti-angiogenic agents might be useful in treating osteoarthritis.