Altered microRNA profile during fracture healing in rats with diabetes

Journal of Orthopaedic Surgery and Research

Shunsuke Takahara¹  Tomoaki Fukui¹  Takahiro Niikura¹  Tomoyuki Matsumoto¹  Takashi Iwakura¹  Etsuko Okumachi¹  Michio Arakura¹  Ryosuke Kuroda¹  Sang Yang Lee¹  Keisuke Oe¹  Takehiko Matsushita¹  Yoshitada Sakai² 

[1] Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine;Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine;

关键词: Diabetes mellitus;    MicroRNA;    Fracture healing;    Delayed union;    Nonunion;   

DOI  :  10.1186/s13018-020-01658-x

来源: DOAJ

【 摘 要 】

Abstract Background MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression. There is increasing evidence that some miRNAs are involved in the pathology of diabetes mellitus (DM) and its complications. We hypothesized that the functions of certain miRNAs and the changes in their patterns of expression may contribute to the pathogenesis of impaired fractures due to DM. Methods In this study, 108 male Sprague–Dawley rats were divided into DM and control groups. DM rats were created by a single intravenous injection of streptozotocin. Closed transverse femoral shaft fractures were created in both groups. On post-fracture days 5, 7, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was conducted with miRNA samples from each group on post-fracture days 5 and 11. The microarray findings were validated by real-time polymerase chain reaction (PCR) analysis at each time point. Results Microarray analysis revealed that, on days 5 and 11, 368 and 207 miRNAs, respectively, were upregulated in the DM group, compared with the control group. The top four miRNAs on day 5 were miR-339-3p, miR451-5p, miR-532-5p, and miR-551b-3p. The top four miRNAs on day 11 were miR-221-3p, miR376a-3p, miR-379-3p, and miR-379-5p. Among these miRNAs, miR-221-3p, miR-339-3p, miR-376a-3p, miR-379-5p, and miR-451-5p were validated by real-time PCR analysis. Furthermore, PCR analysis revealed that these five miRNAs were differentially expressed with dynamic expression patterns during fracture healing in the DM group, compared with the control group. Conclusions Our findings will aid in understanding the pathology of impaired fracture healing in DM and may support the development of molecular therapies using miRNAs for the treatment of impaired fracture healing in patients with DM.

【 授权许可】

Unknown