Bone Abstracts

Dipeptidyl peptidase 4 (DPP4) modulates activity of proteins by removing two aminoterminal amino acids. DPP4 inhibitors are currently being used to improve glucose tolerance in type 2 diabetes patients by increasing the half-life of DPP4 substrates. It has been shown that these substrates do not only increase pancreatic insulin secretion, but also influence bone cell activity. The potential therapeutic effect of DPP4 inhibition on bone metabolism is thus worth being investigat...

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 ...

Introduction: Osteogenesis imperfecta (OI) is characterized by low bone mass, skeletal fragility and, frequently, short stature. We previously showed in oim/oim mice that sclerostin inhibition increased bone mass, mineral content and strength. Here, we compared the body length and the sizes of long bones, head and vertebrae between oim/oim and wildtype mice and analyzed the effect of sclerostin antibody (Scl-Ab) on these parameters.Materials and methods:...

Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signalling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has...

Osteolytic bone disease (OBD) is a frequent complication of multiple cancers, such as multiple myeloma. OBD is due to the disruption of balanced bone remodelling, with higher bone resorption due to increased osteoclast activation and osteoblast inhibition. Lectin–glycoprotein interactions have been implicated in osteoclast formation. In the current study, we set out to identify lectins that are involved in osteoclastogenesis and to study their role in this process. We ant...

: Congenital limb abnormalities represent a prevalence of 0.79/1000 of live births in Massachusetts1. A better understanding of their physiopathology could improve the management of the patients. We report on a 23 weeks female fetus affected by an isolated bilateral terminal transverse defect of the lower limbs with nubbins. Both familial history and chromosomal analyses were irrelevant. We performed a deep morphological examination of the fetus in comparison with a...

Destructive bone lesions due to osteolytic bone disease (OBD) are a major cause of morbidity and mortality in multiple myeloma (MM) patients and the development of new therapeutic strategies is of great interest. In this study, we assessed the effect of SRC inhibition with saracatinib (AZD0530, AstraZeneca) on the development of MM and its associated OBD. We first determined SRC family kinase expression in the MM microenvironment and found that myeloma cells express SRC at low...

Prostate cancer is the most prevalent cancer in men and metastatic spread to bone is detected in up to 80% of patients with advanced disease at autopsy. PCa can progress from treatable androgen-dependent stage to castration-resistant stage with distant metastases for which novel therapeutic targets and strategies are urgently needed. Here we identify the cell surface/secreted oncoprotein Cripto as a potential target for the diagnosis and treatment of metastatic prostate cancer...