Affiliation:
1. State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. China
2. Department of pediatric surgery West China Hospital of Sichuan University Chengdu Sichuan 610041 P. R. China
3. Department of Liver Surgery & Liver Transplantation Center West China Hospital of Sichuan University Chengdu Sichuan 610041 P. R. China
Abstract
AbstractMicroRNAs (miRNAs) regulate several physiological and pathological processes involved in various diseases, including osteoarthritis (OA). OA is the most common global musculoskeletal disorder, characterized by the irreversible progressive destruction of articular cartilage. Supplementation with exogenous miRNAs may represent a promising therapeutic OA treatment, with miRNA‐124 (miR‐124) being a prime candidate for its anti‐inflammatory ability; however, an effective drug delivery system is urgently required to enhance miR‐124 stability and capacity to enter chondrocytes. To this end, tetrahedral framework nucleic acids’ (tFNAs) self‐assembled 3D DNA nanostructures possess superior inherent biocompatibility, versatile functionality, unsurpassed editability, and strong cellular internalization ability. In this study, tFNAs carrying one or three miR‐124 (T‐miR1 or T‐miR3) are successfully synthesized. T‐miR3 is largely absorbed via induced inflammatory chondrocytes by IL‐1β. With reactive oxygen species’ scavenging ability and inflammation‐suppressive miR‐124 release behavior, T‐miR3 efficiently protects chondrocytes against IL‐1β injury in vitro. Additionally, T‐miR3 effectively prevents OA progression by inhibiting chondrocyte apoptosis, smoothing cartilage surfaces, suppressing extracellular matrix degradation, and increasing synovial thickness, effectively protecting in vivo articular cartilage, and illustrating the therapeutic ability of T‐miR3 in OA treatment. This study provides experimental evidence and novel therapeutic strategies for OA treatment in the clinical setting.
Funder
Sichuan University
National Natural Science Foundation of China
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献