Bone Abstracts

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...

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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 ...

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It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

Objective: Chondrolysis, chondrocyte apoptosis, and local inflammation are described to exacerbate osteoarthritis development. We therefore aimed to investigate the effect of adrenomedullin (ADM) and its truncated peptide (22–52ADM) on in vitro and in vivo models. Both have exhibited anti-apoptotic and anti-inflammatory properties in collagen-induced arthritis (CIA) in mice.Methods: In normoxia or hypoxia (physiological condition),...

Human adipose-derived stromal cells (ASCs) exhibit strong plasticity and proliferation potentials. In addition, ASCs are easy to harvest and are found at high frequency in adipose tissue samples. This gives us opportunities for their use in bone regeneration therapy. We thus evaluated the bone formation potential of ASCs in vitro and in vivo.ASCs were isolated from subcutaneous adipose tissue (following Local Ethical Guideline and after...

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...

Background: High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption; is currently evaluated in a phase III clinical trial in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton is a critical question in the context of patients with actively growing skeleton; in particular in the light of our previous studies evidencing that endochondral bone formation was t...

Objective: This work investigated the changes of bone hip structural parameters in obese adolescents enrolled in a successful weight loss program.Methods: Thirty-one obese adolescents (age 13.61±1.27) enrolled in a 8-month weight loss program combining physical activity and nutrition were compared with normal-weight (NW) matched peers (age 15.9±0.43). Investigations were performed at baseline and 8 months. Bone geometric and strength indices we...