Project description:Fracture non-union is a complex clinical condition affecting many patients worldwide; however, known risk factors alone cannot help in predicting individual risk of progressing towards healing complications. The identification of novel biomarkers in the serum of fracture patients is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) that could correlate to the process of fracture healing. Toward this aim, serum of fracture patients and healthy volunteers was screened by RNA sequencing to identify differentially expressed miRNA at different times after injury. The results were correlated to miRNA that were found to be differentially secreted in the conditioned medium of human bone marrow mesenchymal stromal cells (BMSCs) during in vitro osteogenesis.
Project description:The association between DM and impaired fracture healing including delayed union and nonunion has been documented in clinical and experimental settings. We examine miRNA expression specific for impaired fracture healing in diabetic rat.
Project description:Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice. To investigate bone healing in osteoporosis, we performed fracture healing studies in wild-type mice (C57BL/6 genetic background) and the low bone mass strains Col1a1-Krm2 and Lrp5-/- (Schulze et al., 2010; Kato et al., 2002). Osteotomy was set in femora of female mice and stabilized by a semi-rigid fixator to allow fast bone healing (RM-CM-6ntgen et al., 2010). 21 days post surgery we analyzed the fracture calli by biochemical/histological methods, as well as micro-computed tomography, and observed impaired fracture healing in Col1a1-Krm2 and Lrp5-/- mice in comparison to wild-type. To identify genes that may be responsible for the impaired healing in osteoporotic mice, we performed microarray analysis of three independent callus samples of each genotype. The callus tissue was taken 10 days after surgery, because extensive bone formation took place at this point.
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.
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.
Project description:The association between DM and impaired fracture healing including delayed union and nonunion has been documented in clinical and experimental settings. We examine mRNA expression specific for impaired fracture healing in diabetic rat.
Project description:Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized. We used data from microarrays to (1) determine the effects of phosphate restriction on the biologic functions identified from the gene expression in fracture calluses; and (2) examine whether there are genetic differences within the primary biologic functions.
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.