Bone Abstracts

Introduction: Genetic disorders are usually characterised by subjective morphological traits. Mouse models should represent the human situation but it is difficult to translate morphology traits from one species to another. Thus, there is a demand to objectively assess morphological traits. Geometric morphometrics is a mathematical tool to evaluate morphology based on normalised three-dimensional coordinates. Here we use geometric morphometrics to compare the morphology of <em...

Screening gene function in vivo is a powerful approach to discover novel drug targets in the human genome (Nat Rev Drug Discov 2 38–51, 2003). We present data for 3776 distinct gene knockout (KO) mouse lines with viable adult homozygous mice generated using both gene-trapping and homologous recombination technologies. Bone mass was determined from PIXImus DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from ...

Communication between osteoblasts and osteoclasts is crucial for bone remodeling. Thrombin and its thrombin receptor (TR; PAR-1) are expressed in osteoclasts and osteoblasts, respectively. To date, the physiological roles of thrombin and TR in bone metabolism have not been elucidated. Therefore, we fully characterized the bone phenotype of mice lacking the thrombin receptor.We performed bone microarchitectural analyses of the femurs of 10–12 week ol...

Background: Bone metabolic disorders, such as osteoarthritis (OA), osteopenia and osteoporosis have been associated to iron overload, both in humans and animal models. In the case of hereditary hemochromatosis (HH), arthropathy represents one of the most prevalent and disabling symptoms. This work aims at investigating the roles of HH-related HFE mutation and iron accumulation on chondrocyte metabolism.Materials and methods: Primary cultures of articular...

Desbuquois dysplasia (DBQD) is a rare recessive chondrodysplasia, characterized by growth retardation, multiple dislocations and advanced carpal ossification. Two forms of DBQD have been described on the basis of the presence (type 1) or absence (type 2) of characteristic hand anomalies. DBQD type 1 is caused by mutations in the Calcium-Activated Nucleotidase 1 gene (CANT1), while DBQD type 2 is caused by mutations in the xylosiltransferase 1 gene.CANT1 ...

Purpose: Sclerostin, a Wnt inhibitor produced by osteocytes that regulate bone remodelling, might be involved in cartilage metabolism. Therefore, we assessed the effect of sclerostin in osteoarthritis using SOST-deficient mice.Methods: SOST-KO and wild type (WT) mice underwent partial meniscectomie (Mnx). Mice were sacrificed at 4, 6 or 9 weeks after Mnx to analyze i) bone volume (BV/TV) at the femoral condyle, ii) osteophyte volume (microCT), iii) carti...

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 ...

The P2Y2 receptor is a G-protein-coupled receptor and the natural ligands (ATP/UTP) strongly inhibit mineralized bone nodule formation by osteoblasts in vitro. We have earlier shown that overexpression of the P2Y2 receptor in vivo resulted in decreased bone mineral density (BMD), partially due to increased bone resorption, but also decreased formation (detected by serum bone markers and bone histomorphometry).This ...

Receptor activity modifying proteins (RAMPs 1, 2 and 3) are a class of important accessory proteins that interact and regulate several G-protein coupled receptor (GPCR) activity by finely modulating ligand interaction and in some cases trafficking receptors to cell surface.Predominant roles of RAMPs include ligand selectivity in receptors for Calcitonin (CT) family of peptides that comprise calcitonin, calcitonin gene related peptide, amylin and Adrenome...

Objective: In many traumatic or pathological conditions, bone turnover is low and osteoclast activity is reduced or abolished. We developed innovative hydroxyapatite (HA) scaffolds carrying RANKL expressing cells with the aim of supporting bone resorption when this is defective. Membrane-bound (m)RANKL is cleaved into soluble (s)RANKL by MMP14. We hypothesized that the osteoclastogenic potential of RANKL-producing cells could be improved if they were seeded on scaffolds engine...