Bone Abstracts

There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually dimorphic pattern in various physiological systems. We tested the hypothesis that abnormal exposure to steroid hormones within a critical developmental period elicits permanent changes on tooth eruption, enamel mineralization, and leptin and corticosterone concentrations in adulthood. Newborn Wistar rats were divided into four groups, two male groups and two...

Tumor development occurs often by over-activation of members of the RAS-oncogene family (small GTPases (sGTPs)). By blocking the mevalonate pathway, aminobisphosphonates (BPs), and statines prevent activation of GTPs by inhibiting their post-translational prenylation. As we have shown, this induces apoptosis in U2OS osteosarcoma cells by re-activation of FAS expression via epigenetic DNA demethylation (1).The histone demethylase JHD...

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

Introduction: Activated protein C (APC) plays an important role in the cutaneous healing of chronic wounds arising from orthopaedic surgery and has cytoprotective and anti-inflammatory properties which may also assist bone repair. The aim of this study was to examine whether APC could directly influence osteoblasts and increase bone formation in a rodent model.Methods: Proliferation of MG-63 osteoblast-like cells was quantified by MTT assay and direct co...

Mesenchymal stromal cells (MSC) have a potential to differentiate to osteoblasts and adipocytes. Differentiation can be stimulated or inhibited by different growth factors, including fibroblast growth factors (FGFs). In this study we evaluated the effect of FGF2 on the osteoblastic and adipocytic differentiation of MSCs in vitro.Mouse MSC-derived cells were cultured in differentiation medium that led to differentiation to osteoblasts in 14 days ...

Disorders of glucose metabolism are associated with adverse skeletal effects. Hyperglycemia impairs the function of osteoblast-like cells but the mechanisms underlying glucose toxicity are poorly understood. In this study we determined the effect of elevated extracellular glucose levels on the proliferation and osteogenic differentiation of mesenchymal stromal cells (MSC).Bone marrow cells were isolated from rat long bones, plastic-adherent MSCs were enr...

In 1999 Mundy et al. showed that simvastatin, a drug administered for high cholesterol levels, had a profound stimulatory effect on osteoblasts. Since then other studies have also confirmed that simvastatin enhances bone formation; however, the lack of a local delivery system have restricted its clinical use. We have used premixed acidic calcium phosphate cement as a local delivery system for simvastatin. To confirm that the simvastatin released retained its activity,...

Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Little is currently known about what specific factors stimulate osteoblast differentiation from human mesenchymal stem cells (hMSCs). Therefore, the aim for this project is to determine novel factors and mechanisms involved in human bone production which can be targeted to treat osteoporosis, using gene expression profiling and bioinformati...

Background: We have previously shown that MLO-Y4 osteocytes express a number of P2 receptors, respond to a broad range of nucleotides (e.g. UTP) by increasing intracellular calcium concentration and release ATP upon both mechanical and UTP stimulation. The aim of this study therefore is to investigate how the osteocytes release ATP and whether there is a difference in release pathway depending on the type of stimulus.Methods: ATP release was investigated...

The PTH type 1 receptor (PTH1R) is an important modulator of bone remodeling. In mice, PTH1R ablation in osteocytes produces trabecular bone reduction and impaired calcium homeostasis; meanwhile, its overexpression in these cells promotes periosteal and endocortical bone formation. Osteocytes can translate mechanical stimuli into bone-forming signals. Skeletal unloading induces osteocyte apoptosis and bone loss, whereas mechanical stimuli prevent osteocyte apoptosis through in...