Anti-VEGF Therapy in Osteoarthritis and Associated Pain

抗 VEGF 疗法治疗骨关节炎及相关疼痛

基本信息

  • 批准号:
    9124190
  • 负责人:
  • 金额:
    $ 4.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The role of this project is to assess the role of anti-VEGF therapy in osteoarthritis (OA) progression and associated pain. We will assess the use of low dose intra-articular anti-VEGF antibody at the knee joint in a murine OA model, which will be created by destabilization of the medial meniscus (DMM). Intra-articular administration of anti-VEGF antibody will be tested at different time points of OA progression in different groups. We will assess the role of Hyasis(r) Link hydrogel as slow release agent for anti-VEGF antibody. We will selectively silence gene expression of VEGF at chondrocytes using VEGFfl/fl: Aggrecan-CreERT2 transgenic mice, to asses chondrocyte specific role of VEGF associated OA progression and pain. OA progression will be assessed by Safranin-O stained histologic imaging and OARSI scoring. Longitudinal pain behavior will be assessed by mechanical allodynia, using von Frey filament testing. Specific mediators of VEGF mediated OA progression and pain will be assessed by immunofluorescence imaging and immunohistochemistry at the joint surface, synovium, and dorsal root ganglia. Results of this study will assess the potential o anti-VEGF therapy as a disease modifying OA drug as well as potential for targeting OA associated pain.
 描述(由申请方提供):本项目的作用是评估抗VEGF治疗在骨关节炎(OA)进展和相关疼痛中的作用。我们将评估低剂量关节内抗VEGF抗体在小鼠OA模型中膝关节处的使用,该模型将通过内侧半月板(DMM)的不稳定性产生。将在不同组中OA进展的不同时间点测试抗VEGF抗体的关节内施用。我们将评估Hyasis(r)Link水凝胶作为抗VEGF抗体的缓释剂的作用。我们将使用VEGFf 1/f1:聚集蛋白聚糖-CreERT 2转基因小鼠选择性沉默软骨细胞中VEGF的基因表达,以评估VEGF相关OA进展和疼痛的软骨细胞特异性作用。将通过番红-O染色组织学成像和OARSI评分评估OA进展。将使用von Frey细丝测试通过机械异常性疼痛评估纵向疼痛行为。将通过免疫荧光成像和免疫组织化学在关节表面、滑膜和背根神经节评估VEGF介导的OA进展和疼痛的特异性介质。本研究的结果将评估抗VEGF治疗作为疾病改善OA药物的潜力以及靶向OA相关疼痛的潜力。

项目成果

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