Bone Abstracts

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...

The Rab family GTPases Rab27a and Rab27b play an important role in the trafficking of lysosome-related organelles in specialised cells, such as melanocytes. Since secretory lysosomes, also considered a lysosome-related organelle, are important for osteoclast and osteoblast function, we hypothesised that Rab27 plays a role in bone physiology. In support of this, a recent study demonstrated impaired transport of RANK ligand to the plasma membrane in osteoblasts from mice lacking...

Shwachman Diamond syndrome (SDS; MIM 260400) is a monogenic, autosomal recessive, pancreatic condition often accompanied by low bone mass and fracture. In SDS, as in cystic fibrosis, a low bone mass may be secondary to poor nutrition or chronic low-grade infection, but it has also been suggested there may be a primary bone phenotype. Paradoxically, recent studies in cell lines and in a mouse knockout for the SBDS gene, have suggested changes in important osteoclast gr...

The autophagy protein LC3 is necessary for bone resorption by osteoclasts, although it has been suggested that this may be through a novel, autophagy-independent process, by promoting lysosomal fusion at the ruffled border (RB). This process would be analogous to LC3-associated phagocytosis (LAP), in which LC3 is acquired by phagosomes through an autophagy-independent process, and controls phagosome maturation by promoting fusion with lysosomes. We have investigated this possi...

Individuals with type 1 diabetes have over a sixfold increased risk of sustaining a hip fracture compared to the general population. Despite this, bone fragility is not recognized as a classic diabetes-related complication and many diabetes guidelines make no mention of fracture prevention or bone health.We studied bone health in a population of patients with known type 1 diabetes being followed by endocrinologists at an academic centre. Patients filled ...

see PP495....

It is well-established that in vitro differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can recapitulate embryonic development through germ layer induction, enrichment and expansion of specific lineages. We have used PSC technology and developed a novel, mESC differentiation system for investigating the mechanisms of chondrocyte and osteoblast lineage commitment and differentiation. This step-wise, serum-free protocol uses specif...

Paget’s disease of bone (PDB) is a common metabolic bone disease characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Bisphosphonates are highly effective at suppressing bone turnover in PDB but it remains unclear whether greater suppression of bone turnover improves clinical outcome. In the PRISM study, we previously reported that PDB patients randomised to ‘intensive’ treatment aimed at normalising alkaline phospha...

Introduction: Intracellular fat within muscle and visceral tissue has been suggested to adversely influence bone development.Design: We aimed to compare associations between intramuscular and subcutaneous fat and cortical bone outcomes in young adults, in cross-sectional analyses based on the Avon Longitudinal Study of Parents and Children.Method: Data were collected from a research clinic conducted at 17 years of age. Intramuscula...

see PP383....