Bone Abstracts

Background: Skull development is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures that allow rapid bone formation at the edges of the bone fronts. Premature closure of cranial sutures can result in pathological conditions such as Craniosynostosis. The mechanosensory proteins Polycystin 1 (PC1) and 2 (PC2) have been shown to regulate skeletal development and potentially suture formation.Aim: The aim of study w...

Osteosarcoma is the most common primary bone-derived tumor. However, the pathogenic molecular mechanism(s) underpinning osteosarcoma development and metastasis remain elusive. The polycystins PC1 (polycystin-1; encoded by PKD1) and PC2 (polycystin-2) are central players in mechanotransduction, a process that can influence all steps of the invasion/metastasis cascade. Recent studies from our laboratory provided, for the first time, a direct link between mechanosensing polycysti...

Vitamin K is a group name for a number of closely related compounds. Relevant structures for this presentation are phylloquinone (vitamin K1), menaquinone-4 (MK-4) and MK-7. The latter two are members of the vitamin K2 family. The function of all forms of vitamin K is to catalyze the formation of Gla-residues, which are strong calcium-binding groups and essential for the activity of the proteins in which they occur. For calcium metabolism three Gla-proteins are of particular i...

Poor vitamin K intake is associated with markedly increased cardiovascular risk and mortality. The molecular mechanism underlying this association is suggested to be the vitamin K-dependent carboxylation of vascular matrix Gla-protein (MGP), a potent calcification inhibitor. The carboxylation step is essential for its activation, and uncarboxylated MGP, produced during poor vitamin K status, is inactive.The IDS-iSYS inaKtiv MGP assay is the auto...

Pathophysiological calcification in the vasculature favours cardio- and cerebrovascular diseases. In patients with chronic kidney disease vitamin K metabolites are associated with decreased vascular calcification.We investigated the expression of vitamin K dependent proteins (VKDPs) in vessels and bone to identify differences in expression pattern during atherosclerosis (AS) stages and compare the two tissue profiles.Gene expressio...

Objective: Bone fractures are very common in children and their number is growing every year. Vitamin D has a proven role in the prevention of fractures. In the recent study, we have shown that children with low-energy fractures have significantly lower vitamin D blood levels compared to the children without fractures. Our data indicate that higher levels of vitamin D reduced the risk of fracture by 1.06 times (P<0.0005).Past decade has seen...

Gene deletion or treatments with a cathepsin K (CatK) inhibitor in mature preclinical models result not only result in lower bone resorption but also in higher bone formation (BF) on both remodeling and modeling surfaces. Although increased production of clastokines and matrix-derived growth factors may explain the increased BF at remodeling surfaces, the mechanisms for greater BF at modeling surfaces, including the periosteum, remain unexplained. We hypothesized that the abse...

This study is focused on the effects of the synergic use of vitamins D and K on human osteoblasts primary cultures derived from osteoporotic and normal patients. The aim of this work is the evaluation of the different cellular behaviour in response to the lipophilic vitamins stimulation. We included 20 osteoporotic and 20 control patients in age between 35 and 50 and in age between 55 and 85. All patients gave informed consent for using bone samples as a source of bone cells. ...

Objective: Accretion of bone mass in childhood is dependent on both bone modeling and remodeling. We recently found that preosteoclasts secrete platelet derived growth factor type BB (PDGF-BB) to promote angiogenesis coupling with osteogenesis during both modeling and remodeling. As secretion of PDGF-BB by preosteoclasts can be enhanced through inhibition of cathepsin K activity to increase bone mass in adults, we explored if increase of secretion of PDGF-BB by preosteoclasts ...

Introduction: Cathepsin K is necessary for bone matrix resorption. Excessive resorption associated with osteoporosis and osteoarthritis can be reduced by cathepsin K inhibition. MIV-711, a highly selective cathepsin K inhibitor, successfully attenuates both bone resorption and cartilage degradation in non-clinical studies.Aim: To determine safety, tolerability, pharmacokinetics and pharmacodynamics of MIV-711 during multiple oral dosing to postmenopausal...