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MicroRNA-378 suppressed osteogenesis of mesenchymal stem cells and impaired bone formation via inactivating Wnt/β-catenin signaling

By Lu Feng, Jin-fang Zhang, Liu Shi, Zheng-meng Yang, Tian-yi Wu, Hai-xing Wang, Wei-ping Lin, Ying-fei Lu, Jessica Hiu Tung Lo, Da-hai Zhu, Gang Li

Posted 11 Jul 2019
bioRxiv DOI: 10.1101/699355 (published DOI: 10.1016/j.omtn.2020.07.018)

MicroRNAs (miRNAs) served as silencers to repress gene expression at post-transcriptional level. Multiple miRNAs played important roles in osteogenesis. MiR-378 was reported to mediate bone metabolism and influence bone development with the detailed mechanism unknown. 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. Abnormal bone tissues and delayed healing effect were observed in miR-378 TG mice. The osteogenic differentiation of MSCs derived from this TG mouse was also inhibited. We also found that miR-378 mimics suppressed while anti-miR-378 promoted human MSCs osteogenesis. Wnt6 and Wnt10a were identified as bona fide targets of miR-378, which eventually induced the inactivation of Wnt/β-catenin signaling. Finally, the 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 healing process in vivo. In conclude, miR-378 suppressed osteogenesis and bone formation via inactivating Wnt/β-catenin signaling, suggesting miR-378 may be a potential therapeutic target for bone diseases.

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