Anti-VEGF therapy for osteoarthritis and the related pain

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K20068
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Juntendo University
• Principal Investigator: Nagao Masashi 順天堂大学, 革新的医療技術開発研究センター, 講師 (50384110)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 変形性膝関節症 / 血管因子増殖因子 / 軟骨代謝

Outline of Final Research Achievements

Previous study indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA). In this study, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.

Free Research Field

軟骨代謝

Academic Significance and Societal Importance of the Research Achievements

変形性関節症（OA）は関節軟骨の変性と摩耗を経て、関節の変形をきたす疾患である。様々なOA発症の分子機構への理解が深まっているが、現在用いられる薬剤は消炎鎮痛を目的とするものであり、OA進行の抑制あるいは改善をもたらす治療薬の開発が期待されている。本研究を通じて、マウスモデルにおいて、VEGFは膝OAの進行に促進的に働き、抗VEGFの抗体やVEGF阻害薬の投与により膝OAの進行を抑制することが可能であった。今後ヒトにおける膝OAの治療法の候補となりえると考えられる。