School of Chinese Medicine
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.
impaired fracture healing, bioinformatics, miRNA
Source Publication Title
International Journal of Molecular Sciences
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
This work was supported by Natural Science Foundation Council (NSFC 81272045).
Link to Publisher's Edition
He, Bing, Zong-Kang Zhang, Jin Liu, Yi-Xin He, Tao Tang, Jie Li, Bao-Sheng Guo, Aiping Lu, Bao-Ting Zhang, and Ge Zhang. "Bioinformatics and microarray analysis of miRNAs in aged female mice model implied new molecular mechanisms for impaired fracture healing." International Journal of Molecular Sciences 17.8 (2016): 1260.