Searchable abstracts of presentations at key conferences on calcified tissues
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43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

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Oral Communications

Bone mass and bone strength Wnt signalling

ba0005oc2.1 | Bone mass and bone strength Wnt signalling | ECTS2016

Targeted deletion of Wnt1 in mesenchymal cells results in decreased bone mass and spontaneous fractures

Wang Fan , Tarkkonen Kati , Nieminen-Pihala Vappu , Rummukainen Petri , Lehto Jemina , Nagano Kenichi , Baron Roland , Makitie Outi , Kiviranta Riku

Wnt signaling is a major regulator of bone metabolism. We recently reported that mutations in WNT1 gene in humans cause early onset osteoporosis and severe osteogenesis imperfecta. To identify the cellular source and the mechanisms causing these severe phenotypes we generated and analyzed global and conditional Wnt1 knockout mice.Heterozygous Wnt1+/− mice were viable and fertile but Wnt1−/− embryos were lost in ute...

ba0005oc2.2 | Bone mass and bone strength Wnt signalling | ECTS2016

Deletion of Dickkopf-1 in osteoblasts or osteocytes increases bone volume in female mice

Thiele Sylvia , Baschant Ulrike , Thiele Stefanie , Niehrs Christof , Bonewald Lynda , Hofbauer Lorenz C , Rauner Martina

Osteoporosis is a frequent disease leading to an increased risk of fractures caused by a systemic impairment of bone mass, strength, and microarchitecture. Given the emerging role of the Wnt signaling pathway in bone biology, we focused on the function of the important Wnt inhibitor dickkopf-1 (Dkk-1) and examined how the deletion of Dkk-1 solely in osteoblasts or osteocytes influences bone homeostasis. Therefore, we used the Cre-LoxP recombination system and crossed Dkk-1-flo...

ba0005oc2.3 | Bone mass and bone strength Wnt signalling | ECTS2016

Life-course GWAS approach for total body BMD unveils 16 new BMD loci with some exerting age-specific effects

Medina-Gomez Carolina , Kemp John , Chesi Alessandra , Kreiner-Moller Eskil , Harris Tamara , Mook Dennis , Hatwig Fernando , Joro Raimo , Nedeljkovic Ivana , Evans Dan , Mullin Benjamin , Ohlsson Claes , Styrkarsdottir Unnur , Karasik David , McGuigan Fiona , Kiel Doug , Uitterlinden Andre , Tobias Jon , Evans Dave , Rivadeneira Fernando

Introduction: Bone mineral density (BMD) is a highly heritable trait used to assess skeletal health in children and risk of osteoporosis later in life. To date >60 loci associated with bone-related traits measured at different skeletal sites have been identified. We conducted a genome-wide association study (GWAS) meta-analysis of total body (TB-)BMD in children and adults to identify genetic determinants and age-specific effects of loci on this trait.<p class="abstext...

ba0005oc2.4 | Bone mass and bone strength Wnt signalling | ECTS2016

Up-regulation of Wnt antagonists contributes to the attenuated response of bone formation to repeat doses of sclerostin antibody in a mouse model

Holdsworth Gill , Greenslade Kevin , Stencel Zofia , Jose Joby , Kirby Hishani , Moore Adrian , Robinson Martyn , Ke David

Loss of the gene encoding the secreted Wnt antagonist sclerostin results in increased bone mass in humans and mice. Administration of antibodies to sclerostin (Scl-Ab) has been shown to increase bone mineral density (BMD) by increasing bone formation and decreasing bone resorption, in both animal studies and human clinical trials. In these studies, the magnitude and rate of increase in bone formation markers, and the rate of increase of BMD, diminishes upon repeat dosing with ...

ba0005oc2.5 | Bone mass and bone strength Wnt signalling | ECTS2016

Is circulating sclerostin an endocrine modulator of bone mass?

Kulkarni Rishikesh , Schindeler Aaron , Croucher Peter , Little David , Baldock Paul

Mechanosenstitive osteocytes in bone supress the local production of sclerostin in response to mechanical loading, to increase osteoblast differentiation and bone mass. In addition, sclerostin is secreted from osteocytes into the circulation. Serum sclerostin has been shown to correlate with osteoporosis and low bone mass, however there is limited evidence by which to determine whether serum sclerostin is acting either a biomark...

ba0005oc2.6 | Bone mass and bone strength Wnt signalling | ECTS2016

N-cadherin maintains osteoprogenitor number and restrains Wnt signaling in osteoblasts

Fontana Francesca , Salazar Valerie , Brecks Cynthia , Revollo Leila , Mbalaviele Gabriel , Civitelli Roberto

We have shown that genetic ablation of Cdh2 (N−cadherin gene) in osteolineage cells results in osteopenia and decreased osteoprogenitor number. Paradoxically, others have shown that mice overexpressing Cdh2 in osteoblasts are also osteopenic; an action linked to a negative effect of N−cadherin (Ncad) on Wnt signaling, via sequestration of low density lipoprotein receptor−related protein−...