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Profiling microRNA expression in murine bone healing and non-union formation: Role of miR-140 during the early stage of bone healing

Although cellular and molecular mechanisms during the course of bone healing have been thoroughly investigated, the regulation of gene expression by microRNA during bone regeneration is still poorly understood. We hypothesized that nonunion formation is associated with different microRNA expression...

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Published in:PloS one 2019-07, Vol.14 (7), p.e0218395-e0218395
Main Authors: Orth, Marcel, Scheuer, Claudia, Backes, Christina, Keller, Andreas, Rollmann, Mika F, Braun, Benedikt J, Ludwig, Nicole, Meese, Eckart, Pohlemann, Tim, Laschke, Matthias W, Menger, Michael D, Histing, Tina
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cited_by cdi_FETCH-LOGICAL-c692t-c09660da285908a03287a2f4ed3b2923ad37216c123efd69a80c9c3e6252b213
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creator Orth, Marcel
Scheuer, Claudia
Backes, Christina
Keller, Andreas
Rollmann, Mika F
Braun, Benedikt J
Ludwig, Nicole
Meese, Eckart
Pohlemann, Tim
Laschke, Matthias W
Menger, Michael D
Histing, Tina
description Although cellular and molecular mechanisms during the course of bone healing have been thoroughly investigated, the regulation of gene expression by microRNA during bone regeneration is still poorly understood. We hypothesized that nonunion formation is associated with different microRNA expression patterns and that target proteins of these microRNAs are differently expressed in callus tissue of nonunions compared to physiologically healing bones. In a well-established femoral osteotomy model in CD-1 mice osteotomies were induced which result either in healing or in nonunion formation. MicroRNA and target protein expression was evaluated by microarray, quantitative real-time polymerase chain reaction (qrt-PCR) and Western blot. Microarray analyses demonstrated 44 microRNAs to be relevant for nonunion formation compared to physiological bone healing. In nonunions qrt-PCR could validate a higher expression of microRNA-140-3p and microRNA-140-5p. This was associated with a reduced expression of Dnpep and stromal cell-derived factor (SDF)-1α, which are both known to be target proteins of microRNA-140 and also to be involved in the process of bone healing. These data suggest that an increased expression of microRNA-140-3p and microRNA-140-5p markedly contributes to the development of nonunions, most probably by affecting bone morphogenetic protein (BMP)-2 function during the early stage of healing due to a reduced SDF-1α expression.
doi_str_mv 10.1371/journal.pone.0218395
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1932-6203
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source Publicly Available Content Database; PubMed Central
subjects Angiogenesis
Animals
Arthritis
Biochemistry
Biocompatibility
Bioinformatics
Biology and Life Sciences
Biomedical materials
Bone growth
Bone healing
Bone Morphogenetic Protein 2 - biosynthesis
Bone morphogenetic proteins
Bone Regeneration
Bones
Callus
Chemokine CXCL12 - biosynthesis
DNA microarrays
Female
Femur
Femur - injuries
Femur - metabolism
Femur - pathology
Fracture repair
Fractures
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genes
Healing
Laboratory rats
Male
Medicine and Health Sciences
Mice
MicroRNA
MicroRNAs
MicroRNAs - biosynthesis
miRNA
Molecular modelling
Nonunion
Oligonucleotide Array Sequence Analysis
Orthopedic surgery
Osteotomy
Plastic surgery
Polymerase chain reaction
Protein expression
Proteins
Regeneration
Regeneration (physiology)
Research and Analysis Methods
Ribonucleic acid
RNA
RNA polymerase
Time Factors
Trauma
title Profiling microRNA expression in murine bone healing and non-union formation: Role of miR-140 during the early stage of bone healing
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