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 ...

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Objectives: The Brtl mouse, a unique model for the autosomal dominant forms of osteogenesis imperfecta was used to prove the feasibility of a lentiviral-shRNA-based strategy to improve collagen quality by targeting the mutant Col1a1 allele at the point mutation responsible for the causative substitution Gly349Cys. The ability to specifically suppress the mutant allele should convert the moderate Brtl outcome to the mild one caused by quantitative defect.<p class="...

Background: A 5-month-old girl was referred to our unit after a systemic screening for hip dislocation by X-rays revealed bilateral femoral bowing. She was the first child of healthy non-consanguineous parents, and her family history was unremarkable. Her parents had a normal physical examination, and normal laboratory findings. At presentation, her height was 64.0 cm (Z-score: 0.0) with a regular height velocity. Weight was 7.4 kg (Z-score: 1.0). On physical...

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:...

Objectives: Lysophosphatidic acid (LPA) is a potent lipid growth factor which possess several G protein-coupled receptors LPA1-6. We have recently demonstrated that LPA1 receptor-invalidated mice display abnormal bone development and osteoporosis, suggesting abnormal endochondral ossification. We have here further studied the growth plates of LPA1 receptor-invalidated mice.Methods: We performed a microscopic and immuno-histochemistry analysis of the femo...

Objectives: Ghrelin is a peptide hormone secreted in the stomach, which stimulates GH release and food intake. It is also known to have an effect on bone metabolism. The ghrelin specific receptor, GHS-R1a, belongs to the G protein-coupled receptors (GPCRs). Its downstream pathway in osteoblasts remains unclear. We attempted to clarify the way by which ghrelin acts on osteoblast differentiation.Methods: We studied two human osteosarcoma cell lines, MG63 a...

Introduction: Conventional therapy of osteosarcoma, a primary malignant bone tumor, includes surgical excision with wide resection, which leads to physical and aesthetic defects. Allografts for reconstruction of bone and joints and adipose tissue autologous grafts for soft tissue defects can be supplemented with mesenchymal stromal/stem cells (MSCs). Additionally MSCs may be used in tumor-targeted cell therapy. However MSCs may have adverse effects on osteosarcoma development,...

see PP173....

Bone marrow is the main hematopoietic organ of adults. There, hematopoietic stem cells from which all hematopoietic lineages can be generated are preferentially homing. Importantly, bone provides niches for early B cell differentiation and survival of long-lived plasma cells that produced antibodies. Thus, that perturbing bone homeostasis might impact B cell function and antibody production is a highly relevant hypothesis for patients receiving antiresorptive drugs.<p clas...