骨关节炎
受体
软骨
医学
纳米颗粒
药理学
内科学
病理
解剖
材料科学
纳米技术
替代医学
作者
Kaige Ma,Tiep Pham,Jun Wang,InSug O-Sullivan,Amy DiCamillo,Shuxu Du,Fackson Mwale,Zeba Farooqui,Gina Votta-Velis,Benjamin Bruce,André J. van Wijnen,Ying Liu,Hee-Jeong Im
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-16
卷期号:10 (7)
标识
DOI:10.1126/sciadv.adi5501
摘要
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.
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