MicroRNA-378 Suppressed Osteogenesis of MSCs and Impaired Bone Formation via Inactivating Wnt/β-Catenin Signaling

Molecular Therapy: Nucleic Acids

Tian-yi Wu¹  Hai-xing Wang²  Gang Li³  Da-hai Zhu⁴  Jessica Hiu Tung Lo⁵  Zheng-meng Yang⁵  Jin-fang Zhang⁵  Wei-ping Lin⁶  Lu Feng⁷  Ying-fei Lu⁷  Liu Shi⁷ 

[1] Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China;;Laboratory of Orthopaedics &School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, P.R. China;Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, P.R. China;Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China;Traumatology, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China;;Department of Orthopaedics &

关键词: miR-378;    mesenchymal stem cells;    osteogenesis;    Wnt/β-catenin signaling;    bone formation;   

DOI  :  

来源: DOAJ

【 摘 要 】

MicroRNAs (miRNAs) have been reported to serve as silencers to repress gene expression at post-transcriptional levels. Multiple miRNAs have been demonstrated to play important roles in osteogenesis. MicroRNA (miR)-378, a conserved miRNA, was reported to mediate bone metabolism and influence bone development, but the detailed function and underlying mechanism remain obscure. In this study, the miR-378 transgenic (TG) mouse was developed to study the role of miR-378 in osteogenic differentiation as well as bone formation. The abnormal bone tissues and impaired bone quality were displayed in the miR-378 TG mice, and a delayed healing effect was observed during bone fracture of the miR-378 TG mice. The osteogenic differentiation of mesenchymal stem cells (MSCs) derived from this TG mouse was also inhibited. We also found that miR-378 mimics suppressed, whereas anti-miR-378 promoted osteogenesis of human MSCs. Two Wnt family members, Wnt6 and Wnt10a, were identified as bona fide targets of miR-378, and their expression was decreased by this miRNA, which eventually induced the inactivation of Wnt/β-catenin signaling. Finally, the short hairpin (sh)-miR-378-modified MSCs were locally injected into the fracture sites in an established mouse fracture model. The results indicated that miR-378 inhibitor therapy could promote bone formation and stimulate the healing process in vivo. In conclusion, miR-378 suppressed osteogenesis and bone formation via inactivating Wnt/β-catenin signaling, suggesting that miR-378 may be a potential therapeutic target for bone diseases.

【 授权许可】

Unknown