Bone Abstracts

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 (...

Odanacatib (ODN), a selective and reversible cathepsin K inhibitor was shown to histomorphometrically reduce trabecular (Tb) and intracortical (Ic) bone remodeling while preserving endocortical (Ec) and stimulating periosteal (Ps) bone formation (BF) in monkeys. Here, we investigate the bone site specific mechanism of ODN on bone modeling (Mo) versus remodeling (Re)-based osteons. Rhesus monkeys (13–19 yrs, n=8–11/group) were ovariectomized and treated with ...

Background: Mechanical stimulation is thought to be critical for bone anabolic activity. It is unclear how quickly the growing skeleton responds to additional externally-applied mechanical stimuli. We wished to determine the acute effect of a standardised mechanical stimulus to the growing skeleton.Objectives: To determine the acute time course and magnitude of bone’s response to whole body vibration (WBV) in pre-pubertal boys.<p class="abstext"...

Background: Osteogenesis Imperfecta is commonly due to dominant mutations in type I collagen genes, COL1A1 and COL1A2. Recessive forms, which are rarer, are caused instead by mutations in various genes coding for proteins involved in collagen post-translational modifications, folding and secretion. A novel disease locus, SERPINF1, coding for pigment-epithelium-derived-factor (PEDF), a likely key factor in bone deposition and remodelling, has been fou...

In type 2 diabetes mellitus (T2DM) patients, an increased fracture risk is observed, although the bone mineral density is even higher than in non-diabetic patients, which raises the question of the quality of the organic and inorganic matrix in bone1,2. T2DM is also known to favor inflammation of the gingiva and paradontosis in general. However, little is known about the mineral nano-architecture in the mandible and about the possible influence of diabetes. Using sy...