Session Information
Date: Monday, November 13, 2023
Title: (0859–0885) Osteoarthritis & Joint Biology – Basic Science Poster
Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Unbalanced M1/M2 polarization of synovial macrophages plays vital roles in the symptomatic and structural progression of osteoarthritis (OA). The accumulation of intracellular reactive oxygen species (ROS) and the inflammation response cooperatively regulate the phenotype of M1macrophages.The compensatory pathwaysbetween ROS and inflammation in M1macrophages limited the efficacy of treatment regimen modulating a single element (oxidative stress or inflammation). Therefore, we developed a ROS-scavengingand anti-inflammatory agent (licofelone, LCF)-loaded nanoplatform (termed LCF-CSBN) for simultaneously down-regulating inflammatory response and reducing ROS in M1macrophages. The purpose of this study was to investigate the phenotypic reprogramming effect of LCF-CSBN on M1 macrophages and evaluate the efficiency and safety of intraarticular (IA) injection of LCF-CSBN in dealing with OA rat models.
Methods: Cell internalization of LCF-CSBN in M1macrophages was examined by flow cytometry analysis and colocalization study. Scavenging of intracellular ROS were detected by ROS assay kit. RNA sequencing analysis, immunofluorescence (IF) staining, and enzyme-linked immunosorbent assay were performed to measure the mRNA and protein expressions of pathogenic mediators and macrophage polarization markers inM1macrophages treated with LCFand LCF-CSBN. The intra-articular retention time and biodistribution of LCF-CSBN in vivo were evaluated by vivo imaging system and IF staining. Furthermore, LCF-CSBN was injected intra-articularly into the osteoarthritic knee of rats at 3 days after monosodium iodoacetate (MIA) injection and at 5 weeks and 8 weeks after anterior cruciate ligament transection combined with partial medial meniscectomy surgery. Pain behavior assessments, histological analysis, immunohistochemical staining, micro-computerized tomography analysis, and serum enzyme analysis were performed to evaluate the therapeutic effect and safety of IA injection of LCF-CSBN.
Results: Results of RNA sequencing revealed that LCF-CSBN significantly down-regulated the expression of inflammation related genes and reprogrammed the phenotype of M1macrophages. LCF-CSBN was demonstrated to successfully transform M1 macrophages into the M2 phenotype by eliminating cellular ROS and inhibiting expression of inflammatory factors. Additionally, LCF-CSBN was retained in the joint for up to 28 days and selectively distributed into synovial macrophages. In both MIA induced and surgically induced OA rat models, LCF-CSBN effectively and safely relieved pain and suppressed synovial inflammation, as well as alleviated cartilage degradation.
Conclusion: LCF-CSBN has an extended joint-retention time and good capacity of reprogramming the phenotype of synovial M1 macrophages, which exhibits satisfying effect on relieving OA pain and delaying OA progression.Taken together, LCF-CSBN is a promising nanomedicine for OA therapy.
To cite this abstract in AMA style:
Deng C, Xiao Y, Zhao X, Li H, Chen Y, Zeng C, Lei G. Reactive Oxygen Species-scavenging Nanoparticles Target Macrophage Polarization for Osteoarthritis Therapy [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/reactive-oxygen-species-scavenging-nanoparticles-target-macrophage-polarization-for-osteoarthritis-therapy/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/reactive-oxygen-species-scavenging-nanoparticles-target-macrophage-polarization-for-osteoarthritis-therapy/