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Cryo analytical microscopy of cell-mediated mineralization in models of bone disease

Project description

Imaging of bone mineralisation

Bone mineralisation, the deposition of calcium phosphate on the bone matrix, is central for maintaining bone mechanical integrity and remodelling. However, the mechanism by which osteoblasts regulate this process remains poorly understood. The EU-funded BoneImaging project aims to elucidate the process of bone mineralisation during development in unique animal models of bone pathologies. By using state-of-the-art imaging techniques, scientists will investigate alterations in these processes between healthy and pathologic tissues such as in leukaemia or as a consequence of treatment. Results will guide tissue engineering approaches for restoring bone and help identify targeted treatments.

Objective

The bone mineralization process is crucial in maintaining the mechanical integrity of bone, from the time of its development to its constant remodeling throughout life. The process of pathologic mineralization and bone remodeling and how cells control these processes, is very poorly understood in vivo. By characterizing unique animal models of bone pathologies, spanning both lack and increase of bone, this project will elucidate the process of cell-regulated mineralization during endochondral ossification, the mineralization process that occurs during growth of long bones, and also during adult remodeling. We will also investigate how a defect in mineralization affects the mineral content, composition and organization of the collagen fibrils and mineral in pathological bones. We will first map healthy (wildtype) mineralization, focusing on the cell regulated mineralization, mineral composition and structure in bone and calcified cartilage. We will then investigate how the cell regulated mineralization alters in hypomineralized bone models, which have been reported as abnormalities of skeletal development. Finally, we will study the bone remodeling in under and over producing bones in leukemia and
parathyroid hormone (PTH) treated animal models. To address these problems, this work will combine multiscale, state of the art imaging and analysis techniques from dynamic live animal imaging (cellular level) to spatially resolved nanoscale (mineral and collagen fibrils) analytical techniques to characterize the processes by which bone mineralizes, remodels and also any alterations in these processes between healthy and pathologic tissues. Insight into skeletal cellular mineralization mechanisms in pathologic tissues could guide tissue engineering approaches for restoring bone and help to identify targeted treatments.

Coordinator

KING'S COLLEGE LONDON
Net EU contribution
€ 212 933,76
Address
STRAND
WC2R 2LS London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 212 933,76