Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.
Sci Adv
; 10(7): eadi5501, 2024 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-38354243
ABSTRACT
Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these receptors alleviate pain (via VEGFR1) or cartilage degeneration (via VEGFR2). We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII). We demonstrate that a single intraarticular injection of Nano-PAZII can effectively reduce joint pain for a prolonged time without substantial side effects in two different preclinical OA rodent models involving either surgical (upon partial medial meniscectomy) or nonsurgical induction (with monoiodoacetate). The injection of Nano-PAZII blocks VEGFR1 and relieves OA pain by suppressing sensory neuronal ingrowth into the knee synovium and neuronal plasticity in the dorsal root ganglia and spinal cord. Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Fator A de Crescimento do Endotélio Vascular
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article