Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2016) 5 P251 | DOI: 10.1530/boneabs.5.P251

1Heisenberg-Group for Molecular Skeletal Biology, Department of Trauma, Hand & Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Clinic for General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany; 3iBONE Consortium, Germany.

Increasing bone formation is an effective approach to prevent osteoporotic fractures. Although the intermittent administration of PTH is an established osteoanabolic therapy and an anti-Sclerostin antibody (Scle-AB) is currently being tested in phase 3 clinical trials, a great need exists for additional bone anabolic agents. Thus, in the context of a bi-national consortium we aim to uncover novel epigenomic networks controlling bone formation to identify new epigenomic approaches to osteoanabolic therapy. We generated tamoxifen-inducible, osteoblast-specific reporter mice (Osx1-Cre-ERT2;dtTomato) to isolate genetically labeled osteoblasts directly from bones by fluorescent-activated cell sorting (FACS). After tamoxifen injection, adult mice were treated with Scle-AB or vehicle and osteoblasts were enriched from long bones by FACS after collagenase digestion. Of all collected cells, approximately 3% were tomato-positive. Purified osteoblasts were then subjected to epigenome analyses. Therefore, chromatin was isolated followed by an analysis of a set of post-translational histone modifications, including markers of active (H3K4me1, H3K4me3, H3K27ac) and repressed (H3K27me3) genes. Our preliminary results obtained by chromatin immunoprecipitation (ChIP) showed the presence of H3K4me1 on the enhancer of Collagen 1, as well as the constitutively expressed Beta-actin (Actb) gene, but not on the inactive even-skipped homeobox 1 (Evx1) gene. While these analyses confirm the functionality of the experimental system, the ongoing genome-wide massively parallel high throughput sequencing following ChIP (ChIP-Seq) are expected to reveal novel molecular mechanisms regulating bone formation. In conclusion, we have established an in vivo model allowing the investigation of the osteoanabolic epigenomic landscape, which might provide a basis for the development of novel bone anabolic anti-osteoporosis therapies.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

Browse other volumes

Article tools

My recent searches

No recent searches.