Bone Abstracts

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...

Indoxyl sulfate (IS) is one of a number of protein-bound uremic toxins that accumulate in patients with chronic kidney disease. Current conventional hemodialysis is ineffective at removing this toxin. Although IS may impair osteoblast function and induce abnormalities of bone turnover or arthropathy, the effects on knee joint tissue by IS has not been investigated yet. The present studies have been carried out to test the IS effects on synovial fibroblasts, meniscal fibrochond...

Microgravity causes adverse health problems to astronauts during space flight, especially to bone, heart, and muscles. The vascular system plays a central role in various organs and the skeletal tissues. This new environment makes vascular adaptation difficult. Nitric oxide plays an essential role in the vascular system by modulating basal vascular tone. An alteration of NO metabolism or bioavailability has been thought to be one of the main factors for vascular disorders. Res...

The musculoskeletal system experiences severe mechanical strain, with repetitive or extreme strains causing significant trauma; the result being an increase in mechanobiological studies evaluating mechanical strain on musculoskeletal cells. Currently, most stretching studies utilise fibronectin-coated cultures, as these enhance cell attachment. However, recent studies suggest that fibronectin increases cell turnover and DNA damage and affects cell differentiation. Furthermore,...

BA058 is being developed as an anabolic therapy for the treatment of osteoporosis. Daily BA058 SC injection has produced promising safety and efficacy results in early clinical studies, and is currently enrolling in a Phase 3 fracture prevention study. There is, however, a significant need for an alternative to injection that improves patient convenience and compliance. We have investigated the use of a solid Microstructured Transdermal System (3M) for transdermal (TD) deliver...

ASARM peptide (acidic, serine- and aspartate-rich motif) and osteopontin (OPN) fragments accumulate in X-linked hypophosphatemia patients and/or in the Hyp mouse model and, when phosphorylated, potently inhibit mineralization in osteoblast cultures. To investigate this inhibition, we modeled the binding to hydroxyapatite of the human OPN-ASARM peptide (DDSHQSDESHHSDESDEL) using RosettaSurface computational simulations. Peptide binding to hydroxyapatite atomic planes constructe...

Anorexia nervosa (AN) a condition of profound undernutrition, is characterized by alterations in neuroendocrine and metabolic functions. Among the serious pathological consequences of this eating disorder, osteoporosis is often observed and persists after recovery, leading to a high fracture risk.To study particularly bone alterations and recovery, a long term mouse model has been developed. In this model named separation-based anorexia (SBA) – a ch...

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-...

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...