Bone Abstracts

The bioapatite crystals have a multilayer hydrate shell, which contains impurity ions such as magnesium, sodium, potassium and it is not clear the qualitative and quantitative characteristics of noapatite entourage. The major component noapatite environment in bone is water and we studied the surface of nanocrystals from trabecular bone in healthy rats and during the water deficiency.In experiment we use adult laboratory rats (8 months age), remove the c...

To further characterize the role of serotonin (5HT) in bone metabolism, Wistar-Zagreb rat model consisting of the high-5HT and low-5HT subline with different platelet 5HT content and transporter (5HTT) activity has been used.Primary osteoclasts from the high-5HT subline had an increased expression of 5HTT, 5HT–2A receptor, Trap and cathepsin K, while osteoblasts showed no difference in the expression of 5HT elements or osteoblastic markers. However,...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. We report safety, tolerability and biochemistry markers following single ascending dose administration of KRN23 in adults with XLH.Methods: 38 XLH subjects with baseline FGF23≥30 pg/ml were randomized to receive single doses of KRN23 (K) or placebo (P) either (0.003&#15...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 125-dihydroxyvitamin D (125(OH)2D) levels. We report PK and PD of KRN23 following single ascending dose administration in adults with XLH.Methods: 38 XLH patients with baseline FGF23≥30 pg/ml were randomized to receive a single dose of KRN23 (K) or placebo (P) either i.v. (0.003–0.3 mg/kg) or s.c. (0.1–1...

Mutations in PLEKHM1 cause bone disease in humans and animals. Truncations causedeficient bone resorption by osteoclasts leading to osteopetrosis. A gain-of-function point mutation causes increased resorption leading to osteopenia. We and others have shown that PLEKHM1, a multi-modular protein, interacts with the small GTPase rab7 and is involved in vesicle trafficking, secretion, and membrane biogenesis. To investigate other interactions of PLEKHM1 we performed tandem affinit...

Osteoclasts secrete acid and cathepsin K to dissolve the mineral and digest the organic matrix of bone, cartilage and dentine. The secretions are by necessity destructive and potentially harmful to the cell itself and are therefore trafficked through the cell in membrane bound vesicles. Secretion takes place over a specialised membrane compartment, the ruffled border, which is only present in resorbing osteoclasts. The ruffled border membrane and the vesicles in its vicinity h...

Introduction: The fat-soluble and vitamin K2 homologe Menaquinone-7 (MK-7) is needed for post-translational modification of proteins essential in blood coagulation, and in metabolic pathways in various tissues like bone. Recent studies found an association between long-term anticoagulant treatment (OAC) and reduced bone quality due to reduction of active osteocalcin. OAC is often linked to an undesired soft-tissue calcification in both children and adults and may lead to incre...

Molecules secreted by the osteoclast or ‘clastokynes’ are essential to stimulate bone formation by osteoblasts. Treatments with bisphosphates and Denosumab target osteoclast survival and differentiation. This suppresses bone turnover and is suspected to increase the risk of atypical fractures in the long term. A solution to overcome this is to develop strategies that target selectively the activity of osteoclasts without affecting their survival or differentiation. S...

The selective cathepsin K inhibitor odanacatib (ODN) is currently in development for the treatment of postmenopausal osteoporosis. Our goal was to evaluate the effects of ODN vs alendronate (ALN) on bone mass and strength of lumbar vertebrae (LV) in orchiectomized (ORX) rabbits, a model of male osteoporosis. Adult male rabbits (11 months old) were subjected to sham- (n=20) or ORX-surgery (n=24/group) for 7.5 months before dosing initiated. ORX animals were ra...

Gla-rich protein (GRP) is a vitamin K-dependent protein, characterized by a high density of γ-carboxylated Glu residues and high calcium binding affinity. It was shown to accumulate in mouse and sturgeon cartilage and in sites of skin and vascular calcification in humans. Four alternatively spliced transcripts of the GRP gene (GRP–F1, F2, F3 and F4) were described in mouse chondrocytes and zebrafish. Osteoarthritis (OA) is a common degenerative joint disease...