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: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.
