Profiling microRNA expression in murine bone healing and nonunion formation: Role of miR-140 during the early stage of bone healing
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ABSTRACT:
PROVIDER: PRJNA550438 | ENA |
REPOSITORIES: ENA
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Project 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 mi-croRNA-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.
2019-06-27 | GSE133243 | GEO
Project 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.
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Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study explored global RNA expression in remnant bone fragments from acutely injured patients undergoing open primary fracture repair surgery. These data will be compared to blood samples collected from acutely injured subjects, chronic nonunion subjects, and a panel of healthy volunteers. We used microarrays to do a global comparison across bone fragments collected from different patients, and different bones. We also evaluated the role of remnant bone preparation which was either immediate freezing in liquid nitrogen or heat stabilized with the Denator Stabilizer(TM) system.
2017-01-11 | GSE93398 | GEO
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study explored global RNA expression in remnant bone fragments from acutely injured patients undergoing open primary fracture repair surgery. These data will be compared to blood samples collected from acutely injured subjects, chronic nonunion subjects, and a panel of healthy volunteers. We used microarrays to do a global comparison across bone fragments collected from different patients, and different bones. We also evaluated the role of remnant bone preparation which was either immediate freezing in liquid nitrogen or heat stabilized with the Denator Stabilizer(TM) system.
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Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from acutely injured fracture patients collected over multiple days compared to age- and sex-matched healthy volunteers. Bone fragments were collected from acutely injured subjects during surgery through the Cooperative Human Tissue Network-Eastern Division (CHTN-ED http://pathology.med.upenn.edu/research/centers-and-institutes/cooperative-human-tissue-network). We used microarrays to do a global comparison between acutely injured (AI) subjects (AIS) and chronic Nonunion (NU) subjects vs. age- and sex-matched healthy volunteers (HV). We also compared tissue types by capturing bone fragments from the fracture site where possible.
2017-01-11 | GSE93390 | GEO
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from acutely injured fracture patients collected over multiple days to compare normal healers, slow healers, and nonunion outcomes. We used microarrays to do a global comparison between acutely injured (AI) subjects (AIS) vs age and sex matched healthy volunteers (HV) and chronic Nonunion (NU) patients.
2017-01-06 | GSE93217 | GEO
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from acutely injured fracture patients collected over multiple days to compare normal healers, slow healers, and nonunion outcomes. We used microarrays to do a global comparison between acutely injured (AI) subjects (AIS) vs age and sex matched healthy volunteers (HV) and chronic Nonunion (NU) patients.
2017-01-06 | GSE93216 | GEO
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from acutely injured fracture patients collected over multiple days to compare normal healers, slow healers, and nonunion outcomes. We used microarrays to do a global comparison between acutely injured (AI) subjects (AIS) vs. age- and sex-matched healthy volunteers (HV) and chronic Nonunion (NU) patients.
2017-01-11 | GSE93387 | GEO
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from acutely injured fracture patients collected over multiple days to compare normal healers, slow healers, and nonunion outcomes. We used microarrays to do a global comparison between acutely injured (AI) subjects (AIS) vs. age- and sex-matched healthy volunteers (HV) and chronic Nonunion (NU) patients.
2017-01-11 | GSE93378 | GEO
Project description:Profiling of miRNA expressions comparing standard fracture healing models with nonunion models in rats 12w, male, Sprague–Dawley rats were used in this study. Animals were randomized to receive either a surgical treatment that has been shown to produce a nonunion or to a standard stabilized closed femoral shaft fracture that is known to successfully heal. The details of these procedures have been previously described. Briefly, to produce standard healing models, a 1.2-mm diameter K-wire was inserted retrograde into the right femoral intramedullary canal and a closed transverse femoral shaft fracture was produced using a three-point bending apparatus with a drop weight . To produce the nonunion, the fractured site was additionally exposed, and the periosteum was cauterized circumferentially for a distance of 2 mm on each side of the fracture . Five animals from each group were euthanized on post-fracture day 14 for microarray analysis.
2015-09-03 | E-GEOD-55088 | biostudies-arrayexpress