title: Identification of the microRNA transcriptome during the early phases of mammalian fracture repair.
abstract: Fracture repair is a complex process that involves multiple biological processes requiring spatiotemporal expression of thousands of genes. The molecular regulation of this process is not completely understood. MicroRNAs (miRNAs) regulate gene expression by promoting mRNA degradation or blocking translation. To identify miRNAs expressed during fracture repair, we generated murine bone fractures and isolated miRNA-enriched RNA from intact and post-fracture day (PFD) 1, 3, 5, 7, 11, and 14 femurs. RNA samples were individually hybridized to mouse miRNA microarrays. Results indicated that 959 (51%) miRNAs were absent while 922 (49%) displayed expression in at least one sample. Of the 922 miRNAs, 306 (33.2%) and 374 (40.6%) were up- and down-regulated, respectively, in the calluses in comparison to intact bone. Additionally, 20 (2.2%) miRNAs displayed combined up- and down-regulated expression within the time course and the remaining 222 (24%) miRNAs did not exhibit any changes between calluses and intact bone. Quantitative-PCR validated the expression of several miRNAs. Further, we identified 2048 and 4782 target genes that were unique to the up- and down-regulated miRNAs, respectively. Gene ontology and pathway enrichment analyses indicated relevant biological processes. These data provide the first complete analysis of the miRNA transcriptome during the early phases of fracture repair.
authors.affiliation: Department of Life Sciences, Theobald Science Center, Room 420, New York Institute of Technology, Old Westbury, NY 11568-8000, USA. Electronic address: mhadji@nyit.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Hadjiargyrou
authors.affiliation: Bioinformatics Core Facility, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: jizu.zhi.2@stonybrook.edu.
authors.forename: Jizu
authors.initials: J
authors.lastname: Zhi
authors.affiliation: Department of Orthopaedics, HSC T18 Room 85, Stony Brook University, Stony Brook, NY 11794-8181, USA. Electronic address: david.komatsu@stonybrook.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D019295:Computational Biology; D015536:Down-Regulation / Q000235:genetics; D017102:Fracture Healing / Q000235:genetics*; D020869:Gene Expression Profiling; D008297:Male; D008322:Mammals / Q000235:genetics*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs
keywords: Bone; Regeneration; Regulation; Transcriptional; Transcriptome; miRNA