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Int J Mol Sci. 2016 Aug 3;17(8). pii: E1260. doi: 10.3390/ijms17081260.

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

He B1,2, Zhang ZK3, Liu J4,5, He YX6, Tang T7, Li J8, Guo BS9,10, Lu AP11,12, Zhang BT13, Zhang G14,15.

Author information

1
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. hebinghb@gmail.com.
2
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China. hebinghb@gmail.com.
3
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. maxzhangzk@cuhk.edu.hk.
4
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. liujin_hkbu@163.com.
5
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China. liujin_hkbu@163.com.
6
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. berry.he@gmail.com.
7
Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. tangtao@cuhk.edu.hk.
8
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. lijie_bio@126.com.
9
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. boris.g.guo@gmail.com.
10
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China. boris.g.guo@gmail.com.
11
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. aipinglu@hkbu.edu.hk.
12
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China. aipinglu@hkbu.edu.hk.
13
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. zhangbaoting@cuhk.edu.hk.
14
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. zhangge@hkbu.edu.hk.
15
Institute of Integrated Bioinformedicine & Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518000, China. zhangge@hkbu.edu.hk.

Abstract

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.

KEYWORDS:

bioinformatics; impaired fracture healing; miRNA

PMID:
27527150
PMCID:
PMC5000658
DOI:
10.3390/ijms17081260
[Indexed for MEDLINE]
Free PMC Article

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