Bone Abstracts

Objective: Mobility is an important endpoint in patient care with implications for activities of daily living, community participation, and quality of life. We adapted the performance-oriented mobility assessment (POMA-G),1 a widely used and validated clinical gait assessment tool for adults, to use in children with hypophosphatasia (HPP). HPP is the rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue non-specific alkaline phosp...

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts anti-inflammatory effects. It has been implicated in the pathogenesis of several diseases, but its role in the bone microenvironment is still unknown. Here we tested the hypothesis that MFG-E8 also regulates bone metabolism and the development of arthritis.MFG-E8 expression was detected in mouse bones and primary murine osteobl...

Objectives: Glucose-dependent insulinotropic polypeptide (GIP) is secreted by intestinal K-cells into the blood supply in response to nutrient ingestion and absorption. Although osteoblasts and osteoclasts express the GIP receptor (GIPR), the main action of the GIP/GIPR pathway in bone physiology and bone quality is unknown. The aim of the present study was to investigate bone quality in a mouse model of GIPR deficiency.Materials/methods: Eleven 16 weeks...

Proton pump inhibitors (PPIs) are a class of drugs particularly used in gastric disorders. They promote a decrease on gastric acid secretion by inhibiting the H+/K+ ATPases. Osteoclasts are cells specialized in bone resorption by H+ translocation to the bone surface. Thus, PPIs might be regarded as potential tools to modulate osteoclast resorption activity, particularly in conditions that are associated with a hyperactivation of osteoclasts, li...

Differentiation of osteoclast progenitor cells into mononucleated TRAcP+ pre-osteoclasts occurs in the bone marrow. But how are these cells dispatched to the future bone resorption sites? We hypothesized that the collagen type III/I-rich reticulin network of the bone marrow might provide a structural framework for localization and migration of differentiating pre-osteoclasts towards the bone surface. Therefore, adjacent sections from decalcified paraffin-embedded iliac crest b...

In light of prolonged life expectancy, the need for biomaterials that govern bone regeneration increases. Improved bone regeneration and osseointegration can be achieved by funtionalizing implant materials. The extracellular matrix (ECM) affects differentiation of bone cells and is critical for bone regeneration. Here we assessed the role of the natural occurring bone ECM glycosaminoglycans (GAGs) hyaluronan (HA) and chondroitin sulfate (CS), and their sulfated derivatives, on...

Osteoclast (OC)-mediated bone destruction is a key feature of rheumatoid arthritis (RA). In RA synovial tissue a reduced density of catecholaminergic nerve fibres has been observed. Studies on sweat gland innervation proved that catecholaminergic fibres have the ability to undergo a phenotypic transition to cholinergic nerves. The sympathetic neurotransmitters norepinephrine (NE), acetylcholine (ACh), and vasoactive intestinal peptide (VIP) affect osteoclastogenesis oppositely...

Despite its importance, the resorptive surface of osteoclasts has not been directly visualised. We exploited a novel approach that enables us to inspect the substrate-apposed surface of cells. To achieve this, we incubated osteoclasts on vitronectin-coated nail varnish and, afterwards, we dissolved the substrate and visualised the cells resorbing-side up in the scanning electron microscope (SEM). We then employed confocal microscopy to correlate the SEM appearances with the di...

Periodontitis is an inflammatory disease that affects connective tissue attachments and the supporting bone that surrounds the teeth. Periodontal ligament fibroblasts induce the overexpression of matrix metalloproteinase (MMP), which is involved in inflammatory progression in periodontitis. Osteoclasts are responsible for skeletal modeling and remodeling but may also destroy bone in several bone diseases, including osteoporosis and periodontitis. This study examined the anti-d...

Odanacatib (ODN) is an orally-active cathepsin K inhibitor being developed for the treatment of postmenopausal osteoporosis. This study evaluated the effects of ODN 50mg once weekly on BMD, bone turnover markers and safety in patients previously treated with alendronate (ALN).This was a randomized, double-blind, placebo-controlled, 24-month study. The primary endpoint was % change from baseline at month 24 of femoral neck (FN) BMD. Postmenopausal women (...