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Int. J. Mol. Sci. 2016, 17(8), 1260;

Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing

1,2,* , 3,* and 1,2,*
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Constantinos Stathopoulos
Received: 3 June 2016 / Revised: 24 July 2016 / Accepted: 29 July 2016 / Published: 3 August 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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Impaired fracture healing in aged females is still a challenge in clinics. MicroRNAs (miRNAs) play important roles in fracture healing. This study aims to identify the miRNAs that potentially contribute to the impaired fracture healing in aged females. Transverse femoral shaft fractures were created in adult and aged female mice. At post-fracture 0-, 2- and 4-week, the fracture sites were scanned by micro computed tomography to confirm that the fracture healing was impaired in aged female mice and the fracture calluses were collected for miRNA microarray analysis. A total of 53 significantly differentially expressed miRNAs and 5438 miRNA-target gene interactions involved in bone fracture healing were identified. A novel scoring system was designed to analyze the miRNA contribution to impaired fracture healing (RCIFH). Using this method, 11 novel miRNAs were identified to impair fracture healing at 2- or 4-week post-fracture. Thereafter, function analysis of target genes was performed for miRNAs with high RCIFH values. The results showed that high RCIFH miRNAs in aged female mice might impair fracture healing not only by down-regulating angiogenesis-, chondrogenesis-, and osteogenesis-related pathways, but also by up-regulating osteoclastogenesis-related pathway, which implied the essential roles of these high RCIFH miRNAs in impaired fracture healing in aged females, and might promote the discovery of novel therapeutic strategies. View Full-Text
Keywords: impaired fracture healing; bioinformatics; miRNA impaired fracture healing; bioinformatics; miRNA

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He, B.; Zhang, Z.-K.; Liu, J.; He, Y.-X.; Tang, T.; Li, J.; Guo, B.-S.; Lu, A.-P.; Zhang, B.-T.; Zhang, G. Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing. Int. J. Mol. Sci. 2016, 17, 1260.

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