Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

作者：Kaige Ma, Gurjit Singh, Jun Wang, InSug O‐Sullivan, Gina Votta‐Velis, Benjamin Bruce, Arivarasu Natarajan Anbazhagan, André J. van Wijnen, Hee‐Jeong Im · 发表于：International Journal of Biological Sciences · 年份：2023 · DOI：10.7150/ijbs.79125 · 被引用次数：34 · 研究领域：Osteoarthritis Treatment and Mechanisms、Angiogenesis and VEGF in Cancer、Inflammatory mediators and NSAID effects

using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.