ECTS2016 Poster Presentations Genetics and Epigenetics (25 abstracts)
Investigating the osteoanabolic epigenome of aging-related bone loss in humans
Matthias Ring 1, , Hiroaki Saito 1, , Hanna Taipaleenmäki 1, , Zeynab Najafova 2, , Katharina Jähn 1, , Andreas Gasser 1, , Carl Haasper 3 , Roland Gessler 3 , Thorsten Gehrke 3 , Steven A. Johnsen 2, & Eric Hesse 1,
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; 3HELIOS ENDO Hospital Hamburg, Hamburg, Germany, 4iBONE Consortium, Germany.
During aging bone resorption often increases while bone formation decreases, thereby reducing bone mass and bone mineral density (BMD) and leading to osteoporosis. Evidence suggests that extrinsic factors may influence bone remodeling. While poorly understood, these mechanisms may function by inducing epigenomic programs that diminish the bone forming capacity of osteoblasts. This study is part of a bi-national consortium aimed at uncovering epigenomic networks controlling the aging-related decrease in bone formation. To reach this goal, we collected human femoral heads from elderly (65–85 years) and young (25–45 years) patients undergoing hip replacement. To characterize the material, clinical parameters affecting bone metabolism (e.g. history of falls, diseases and vitamin D level) were obtained. So far, samples from 45 patients with an average age of 60 years were harvested. Interestingly, 98% had a vitamin D deficiency. Imaging of a well-defined part of the femoral head by μCT showed an approximately 10% reduction in bone mass and BMD in the elderly compared to the young group. Chromatin immunoprecipitation (ChIP) assays of intact bone tissue demonstrated a selective and specific enrichment of the active chromatin marks H3K4me3 H3K27ac on several osteoanabolic genes, including Runx2, ALP and Collagen1. Next, the sample number will be increased and all specimens will be analyzed by μCT and bone histomorphometry. Results will then be combined with clinical data and laboratory results. We will then identify epigenetic regulatory pathways controlling aging-related bone loss by analyzing gene expression (RNA-seq), genome-wide DNA methylation (MeDIP) and a selected set of post-translational histone modifications (ChIP-seq) known to control osteoblast differentiation, precursor cell fate and lineage-specific gene expression. Together, our results demonstrate the feasibility of identifying epigenetic regulation of physiologically important osteoanabolic genes from human bone samples by epigenome mapping. This may lead to the development of new drugs for the treatment of aging-related bone loss.
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Bone Abstracts
ISSN 2052-1219 (online)
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