Senescence-targeted MicroRNA/Organoid composite hydrogel repair cartilage defect and prevention joint degeneration via improved chondrocyte homeostasis  

作　　者：Ye Sun Yongqing You Qiang Wu Rui Hu Kerong Dai 

机构地区：[1]Department of Orthopaedics,The First Affiliated Hospital of Nanjing Medical University,Jiangsu,210029,China [2]Shanghai Key Laboratory of Orthopaedic Implants,Department of Orthopaedic Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,China [3]Renal Division,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing,China

出　　处：《Bioactive Materials》2024年第9期427-442,共16页生物活性材料（英文）

基　　金：funded by the China National Natural Science Funds(No.82172446).We are also grateful for the help and advice from Professor Kerong Dai from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University。

摘　　要：Introduction:Cartilage defect(CD)is a common complication in osteoarthritis(OA).Impairment of chondrogenesis and cellular senescence are considered as hallmarks of OA development and caused failure of cartilage repair in most clinical CD cases.Exploring markers for cellular senescence in CD patients might provide new perspectives for osteoarthritic CD patients.In the present study,we aim to explore senescent markers in CD patients with OA to fabricate a senescence-targeted SMSC organoid hydrogel for cartilage repair.Methods:Clinical cartilage samples from cartilage defect patients were collected.Immunofluorescence staining of senescent markers and SA-β-Gal staining were used to detect the senescence state of SMSCs and chondrocytes in cartilage defect and OA patients.MicroRNA expression profiles of SMSC organoids and H2O2-treated SMSC organoids were analyzed and compared with high-throughput microRNA sequencing.Fluorescent in situ hybridization of miRNA were used to determine the expression level of miR-24 in SMSC organoids and cartilage samples.Interaction between miR-24 and its downstream target was analyzed via qRT-PCR,immunofluorescence and luciferase assay.Senescence-targeted miR-24μS/SMSC organoid hydrogel(MSOH)was constructed for cartilage repair.Anti-senescence properties and chondrogenesis were determined in vitro for MSOH.Rats were used to evaluate the cartilage repair capacity of the MSOH hydrogel in vivo.Results:In this study,we found Osteoarthritic cartilage defect patients demonstrated upregulated cellular senescence in joint cartilage.MicroRNA sequencing demonstrated senescence marker miR-24 was negatively associated with cartilage impairment and cellular senescence in osteoarthritic CD patients.Moreover,miR-24 mimics alleviates cellular senescence to promote chondrogenesis by targeting downstream TAOK1.Also,miR-24 downregulated TAOK1 expression and promoted chondrogenesis in SMSC organoids.Senescence-targeted miR-24μS/SMSC organoid hydrogel(MSOH)was constructed and demonstrated superior chondrog

关 键 词：CARTILAGE DEGENERATION CHONDROCYTE 

分 类 号：R318.08[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]