机构地区:[1]Department of Sports Medicine,Peking University Shenzhen Hospital,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,518036,China [2]Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration,Shanghai,201306,China [3]Department of Orthopedics,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,200233,China [4]Department of Orthodontics,Shanghai Stomatological Hospital&School of Stomatology,Fudan University,Shanghai,200001,China [5]Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases,Fudan University,Shanghai,200001,China [6]Minhang Hospital,Fudan University,Shanghai,201199,China
出 处:《Bioactive Materials》2023年第12期169-183,共15页生物活性材料(英文)
基 金:the Key Project of National Natural Science Foundation of China(81830076);the National Natural Science Foundation of China(82272568);the Shanghai Engineering Technology Research Center and Professional Technology Service Platform project of 2020“Science and Technology Innovation Action Plan”of Shanghai(20DZ2254100);the Biomedical Technology Support Special Project of Shanghai 2021“Science and Technology Innovation Action Plan”(21S31902300).
摘 要:Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic strategy.In this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic effect.miR-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting.For enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage.The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of OA.This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.
关 键 词:OSTEOARTHRITIS Extracellular vesicles NLRP3 inflammasome PYROPTOSIS Cartilage-targeting
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