Bone Abstracts

see PP288....

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 ...

It is still unknown where from osteoblasts are recruited during remodeling of adult human cancellous bone. Still, it is often suggested that they originate from perivascular osteoprogenitors in the bone marrow (BM). Here we propose also the existence of a layer of osteoprogenitors at the periphery of the BM. This proposal is based on electron and light microscopy of the bone surface and of the neighboring BM in human iliac crest biopsies, where we quantified cell densities, ce...

Small GTPases of the Rho family (RhoA and Rac-1) are responsible for cytoskeleton dynamics (particularly actin polymerisation) and control cellular tension. For these reasons, they are implicated in the commitment of multipotent cells (MCs). In one hand, increased tension (important RhoA activity) is commonly associated with osteogenesis (OS), in the other hand, a reduced one (low RhoA activity) is associated with adipogenesis (AD). Nevertheless, precise RhoGTPases regulations...

Osteoblastic MMPs are important actors of bone remodeling. We showed previously that osteoblast specific overexpression of TIMP1, an inhibitor of MMPs, prevents the bone loss induced by ovariectomy mainly through inhibition of bone resorption. We hypothesized that inhibition of the MMP3 could be implicated in the protective effect of TIMP1 and that MMP3 polymorphisms located in the proximal promoter of MMP3 gene could be associated to post-menopausal bone loss in women.<p ...

Improvements on the overall cure rates for childhood acute lymphoblastic leukemia (ALL) have allowed the cure of over 85% of treated patients. At least 70% of survivors of childhood ALL cancers have substantial morbidities as a result of their treatment. Long term musculoskeletal complications in this population are currently receiving increasing attention because of their negative impact on the quality of life and ability to perform appropriate activities. Our objective was t...

Background: Cancer patients often receive a combination of drugs that target both the microenvironment and the tumour cells. However, the role of the bone microenvironment (BME) in mediating peripheral breast cancer growth remains poorly understood. This is the first study to determine whether reduced subcutaneous tumour growth following combination therapy is due to direct interactions between the drugs and tumour cells or through zoledronic acid induced alterations to the BM...

Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects by translocating to the nucleus and there affects gene transcription, but some effects can also be mediated via extra-nuclear actions of the receptor by, e.g., triggering cytoplasmic signaling cascades. ERα contains various domains and the role of activation functio...

see P393....

Melatonin is a neuro-hormone released primarily from the pineal gland, which has been shown to have bone anabolic effect, although it is still unclear whether its skeletal action is directly mediated by receptors expressed on bone cells or is indirect. In this study, we examined melatonin’s effects on bone cellular activities in vitro and tested whether it modifies angiogenesis and blood flow to bone, which are both essential for bone formation.<p class="abst...