Bone Abstracts

Background: Treatment with multipotent mesenchymal stromal cells (MSC) has the potential to ameliorate mesodermal disorders.Objective: To treat severe osteogenesis imperfecta (OI) with fetal MSC.Methods: Ten years ago, we treated a fetus with OI type III (COL1A2: c.3008G>A, p.Gly1003Asp) in utero with fetal HLA-mismatched MSC. The procedure was uncomplicated. At the age of 4 months i.v. pamidronete treatment was starte...

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...

Introduction: Dentinogenesis imperfecta (DI) is a common dental aberration in patients with osteogenesis imperfecta (OI). Mutations that cause abnormal collagen chains will cause more serious types of OI and it has been claimed that DI should be a marker for qualitative defected collagen. It has also been supposed that normal development of teeth may be more dependent on normal α2(I) than normal α1(I) chains which are encoded by COLIA2 and COLIA1 ge...

Abstract: Osteogenesis imperfecta, also known as ‘brittle bone disease’, is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study, small interfering RN...

The selective cathepsin K inhibitor odanacatib (ODN) is currently in development for the treatment of postmenopausal osteoporosis. Our goal was to evaluate the effects of ODN vs alendronate (ALN) on bone mass and strength of lumbar vertebrae (LV) in orchiectomized (ORX) rabbits, a model of male osteoporosis. Adult male rabbits (11 months old) were subjected to sham- (n=20) or ORX-surgery (n=24/group) for 7.5 months before dosing initiated. ORX animals were ra...

Molecularly characterized epigenetic networks that control bone formation and are altered during aging are necessary to uncover new potential targets for osteoanabolic therapy. Our contribution to the iBONE consortium is to identify osteoanabolic epigenomic regulators by screening which are involved in osteoblast phenotype and differentiation. This study will be done by a 3 step approach including: siRNA screening for epigenomic regulators of osteoblastic differentiation and v...

Introduction: FGF-21 is a protein that is produced by the liver and adipocytes. In patients with anorexia nervosa (AN), it could be involved in a complex adaptive response to starvation. In addition, this newly discovered protein could play pathogenic role in trabecular skeletal homeostasis. The aim of our work was to evaluate the concentrations of FGF-21 and bone metabolism in patients with AN.Methods: Thirty seven female patients (aged 14.76±3.99 ...

The cathepsin K inhibitor odanacatib (ODN) is a bone formation-sparing inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. To support the bone safety profile of ODN, we evaluated the effects of ODN on trabecular bone hard tissue properties in the estrogen-deficient model of the ovariectomized (OVX) rhesus monkeys. Animals (n=16/group, age 11–22 years) were treated immediately af...

Osteosarcoma is the main malignant primary bone tumor in children and adolescents for whom the prognosis remains poor, especially when metastases are present at diagnosis (survival rate drops to 20% when lung metastases were detected). Because TGF-β has been shown to promote metastases in many solid tumors, we investigated the effects of inhibition of the TGF-β/Smad cascade on osteosarcoma behavior. To this end, two independent procedures, a pharmacological approach ...

Interleukin- 34 (IL34) is a new, challenging cytokine discovered in 2008. It promotes the proliferation, survival and differentiation of the monocyte/macrophage lineage with almost the same efficiency as the macrophage-colony stimulating factor (M-CSF). IL34 has already been described to play a key role in various musculoskeletal bone diseases such as bone giant cell tumors or in rheumatoid arthritis. These ‘twin’ cytokines share a lot of functional similarities whic...