Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures
Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients.
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:The objective of this study was the identification of serum microRNAs that can differentiate osteoporotic fracture patients with and without type-2 diabetes from healthy control subjects. For that purpose circulating microRNAs were profiled by real-time quantitative PCR using a custom 384-well panel in 200 µl serum samples. Univariate and multivariate statistical tools were used in order to identify single as well as combinations of circulating microRNas that were characteristic of patients with prevalent osteoporotic fractures: a qRT-PCR-based classifier consisting of miR-550a-5p, miR-96-5p, miR-32-3p and miR-486-5p can distinguish T2D women with (DMFx) and without fragility fractures (DM) with high specifitiy and sensitivity (AUC = 0.93). A classifier consisting of miR-188-3p, miR-382-3p, miR-942 and miR-155-5p was capable of differentiating between postmenopausal women with osteoporotic fractures and fracture-free controls with an AUC of 0.98.
Project description:This study aims to identify specific miRNAs profiles in osteoporotic patients with and without vertebral fractures. MiRNAs array analysis was performed on the plasma samples including a pool of 6 miRNA samples from osteoporotic patients with vertebral fractures, a pool of 6 miRNA samples from osteoporotic patients without fracture and another pool of 6 miRNA samples from nonosteoporotic patients to identify regulated miRNAs in the plasma.
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:SD rats were intramuscular injected with dexamethasone to induce osteoporosis, and treated with APS. Then, colonic epithelia of control, osteoporotic and APS-treated osteoporotic rats were collected for MethylC-capture sequencing .