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: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.
Project description:Current clinical approaches to promote osteoporotic fracture healing primarily target osteoclast biology, overlooking the negative regulatory role of fibroblasts in fracture healing. Perioperative bisphosphonates (BPs) used in anti-osteoporosis treatment for osteoporotic fractures have become a consensus worldwide. However, excessive fibrosis is induced simultaneously, leading to fracture non-union and atypical femur fractures. It is highly desirable to inhibit osteoclasts but block fibrosis. In this study, an magnesium ions (Mg2+)-BPs MOF-based bone adhesive material was designed to down-regulate SOST and weaken SOST/TGF-β signaling pathway through Mg2+ through transcriptome analysis, thus inhibiting fibrotic differentiation and subsequent disordered mineralization.
Project description:Osteoporotic fractures are notoriously difficult to heal due to an imbalance between osteoblasts and osteoclasts. Current treatments often have limited efficacy or adverse side effects, highlighting the need for safer, more effective solutions. Here, we developed an injectable plant-derived phosphate coordination compound-based adhesive hydrogel to restore bone homeostasis by integrating magnesium ions (Mg2+)-phytic acid (PA) nanoparticles with aminated gelatin and aldehydated starch. The hydrogel can firmly adhere to irregular bone tissue at the fracture site and achieve achieve Mg-PA degradation in response to the osteoporotic acidic microenvironment, releasing PA and Mg2+, which modulated osteoclast and osteoblast activity, respectively. Impressively, PA inhibits osteoclastogenesis by stimulating monocyte secretion of CCN1, which competitively binds RANKL to disrupt RANKL-RANK signaling. Meanwhile, Mg2+ enhances osteoblast differentiation from bone marrow stem cells. In an ovariectomized rat model, the hydrogel significantly accelerates fracture healing (84.63% improvement over the control groups in flexural strength). This study highlights the potential of PA-based coordination compounds as a novel strategy for osteoporotic fracture treatment.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.