Bone Abstracts

In 1999 Mundy et al. showed that simvastatin, a drug administered for high cholesterol levels, had a profound stimulatory effect on osteoblasts. Since then other studies have also confirmed that simvastatin enhances bone formation; however, the lack of a local delivery system have restricted its clinical use. We have used premixed acidic calcium phosphate cement as a local delivery system for simvastatin. To confirm that the simvastatin released retained its activity,...

Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Little is currently known about what specific factors stimulate osteoblast differentiation from human mesenchymal stem cells (hMSCs). Therefore, the aim for this project is to determine novel factors and mechanisms involved in human bone production which can be targeted to treat osteoporosis, using gene expression profiling and bioinformati...

Background: We have previously shown that MLO-Y4 osteocytes express a number of P2 receptors, respond to a broad range of nucleotides (e.g. UTP) by increasing intracellular calcium concentration and release ATP upon both mechanical and UTP stimulation. The aim of this study therefore is to investigate how the osteocytes release ATP and whether there is a difference in release pathway depending on the type of stimulus.Methods: ATP release was investigated...

The PTH type 1 receptor (PTH1R) is an important modulator of bone remodeling. In mice, PTH1R ablation in osteocytes produces trabecular bone reduction and impaired calcium homeostasis; meanwhile, its overexpression in these cells promotes periosteal and endocortical bone formation. Osteocytes can translate mechanical stimuli into bone-forming signals. Skeletal unloading induces osteocyte apoptosis and bone loss, whereas mechanical stimuli prevent osteocyte apoptosis through in...

Strontium ranelate (SrRan) is an efficient treatment for osteoporosis, because SrRan both inhibits osteoclasts and stimulates osteoblastic bone formation. We have previously shown that SrRan also affects mouse osteocyte signaling towards osteoclast precursors and mature osteoblasts. This study assessed the effect of SrRan on paracrine signaling from mechanically-stimulated human osteocytes towards mesenchymal stem cells.Human primary bone cells, used as ...

Osteocytes make up >90% of bone cells, are embedded in mineralised matrix where they form a communication network. Osteocytes differentiate from osteoblasts, and are mechano-sensitive. They are very difficult to isolate with a dependence on cell lines for in vitro studies of osteocyte biology. Therefore new methods to study these cells are essential. Recent publications indicate that osteoblasts maintained in in vitro 3D collagen gels may differentiate to...

Formation and growth of long bones occur through the process of endochondral ossification, which depends on proliferation and hypertrophy of chondrocytes in growth cartilage. In a subtractive hybridization study of equine cartilage, we recently identified a number of genes, the roles of which in growth cartilage have not been characterized. A subset of these genes was found to be differentially expressed between the zones of equine growth cartilage. The genes encoding ATPase H...

Calcium represents one of the most versatile and universal signalling particles regulating many different cellular processes. Changes in [Ca2+]i give rise to a vast diversity of modulatory events, amongst others, influencing activities of kinases and ion channels.It was demonstrated that nuclear magnetic resonance therapy (NMRT) treatment in osteoarthritis led to reduced pain and improved function followed by increase in quality of ...

Introduction: Using transgenic mice ectopically expressing Hoxa2 all along chondrogenesis, we previously associated the resulting animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was due to a negative influence of Hoxa2 in the very first step of endochondral ossification. As the molecular pathways underlying this pathogenesis are still unknown, we here tried to identify the impact of Hoxa2 overexpression on ...

Background: Cartilage matrix breakdown in osteoarthritis (OA) is due to mechanical stress and inflammation leading to increased metalloproteinases (MMPs) production. Currently, IL1β is thought to have a major role in this process. IL1β is synthesized as an inactive precursor, which is cleaved into the secreted active form. This maturation process mainly occurs in the inflammasome complex. Inflammasome is constituted by initiators (including NALP3) and adaptor molecul...