MicroRNA-144-3p inhibits bone formation in distraction osteogenesis through targeting Connexin 43
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Yu-Xin Sun1,2,3,*, Jin-Fang Zhang2,3,*, Jia Xu4, Liang-Liang Xu2, Tian-Yi Wu2, Bin Wang2, Xiao-Hua Pan1 and Gang Li1,2,3,5
1Department of Orthopaedics and Traumatology, Bao-An District People’s Hospital, Shenzhen, PR China
2Department of Orthopaedics & 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, PR China
3The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China
4Department of Orthopaedics Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, PR China
5Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China
*These authors have contributed equally to this work
Xiao-Hua Pan, email: [email protected]
Gang Li, email: [email protected]
Keywords: distraction osteogenesis, mesenchymal stem cells, microRNAs, miR-144
Received: July 14, 2017 Accepted: August 17, 2017 Published: September 18, 2017
Distraction osteogenesis (DO), one of effective therapies for bone regeneration, has been received more attention in recent years. However, the underlying mechanism remains elusive. Recently, microRNAs (miRNAs) have been reported to play important roles in regulating osteogenesis and bone formation. We therefore provided the hypothesis that miRNAs could involve in the DO-mediated bone regeneration. After successfully established the DO model of rats, a miRNA microarray was performed to find the differently expressed miRNAs in DO and control groups in this study. As one of the most downregulated miRNAs, miR-144-3p was found to be decreased during osteogenic differentiation in mesenchymal stem cells of rats (rBMSCs) and DO model. And miR-144-3p overexpression suppressed the osteogenesis while its inhibitor promoted osteogenesis. Furthermore, Connexin-43, an essential regulator for osteogenesis, was validated to be a novel target for miR-144-3p. Finally, miR-144-3p inhibitor modified MSCs promoted mineralization of distracted bone in rat DO model. In conclusion, miR-144-3p was found to regulate osteogenesis and inhibition of miR-144-3p resulted in acceleration of mineralization of DO, which not only give clues to understanding the mechanism of DO but also provide a potential therapeutic target in clinical practice.
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