title: Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.
abstract: BACKGROUND
  Angiogenesis 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.
  
  
  METHODS
  First, 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).
  
  
  RESULTS
  Histologically, 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.
  
  
  CONCLUSIONS
  Considering 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.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Masato
authors.initials: M
authors.lastname: Sato
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Munetaka
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tani
authors.forename: Joji
authors.initials: J
authors.lastname: Mochida
mesh_terms: D053674:Aggrecans / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D000068258:Bevacizumab; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D054850:Osteophyte / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D053674:Aggrecans; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D024043:Collagen Type II; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab