Objectif Osteoporosis is an age and gender-related condition characterised by reduced bone mass, impaired micro-architecture and increased risk of low-trauma fractures. Osteoporosis-related fractures are a major health concern and impose a huge economic burden on European health care systems. In the young, bone adapts its mass and architecture in response to strains engendered by mechanical loading. However, this response in blunted in the aged. We have shown that the anabolic response to load is similarly impaired in an age and gender-related manner in mice. Counter-intuitively, this response can be “rescued” in aged female mice if short periods of loading are imposed against a background of disuse rather than activity. We hypothesise that this “rescue” involves increased recruitment of bone forming osteoblasts. The primary objective of this proposal is, to establish whether the age and gender-related decline in bone’s adaptive response to mechanical loading in mice can be attributed to insufficient recruitment of osteoblasts necessary to form new bone and, if so, whether this deficiency can be “rescued” by appropriate manipulation of bones’ loading environment. To achieve the objectives in this proposal, we will investigate bones from aged male and female mice, which have been subjected to mechanical loading with or without prior disuse. These will be compared with similarly treated bones of young mice. Our studies should further elucidate the mechanisms underlying the age-related decline in bones’ adaptive response to mechanical loading. We hope that these studies could identify novel therapeutic targets to augment bones’ natural anabolic response to physical activity/loading. This could be of particular relevance in maintaining bone mass in situations of aging, paralysis or even space flight. The proposal will strengthen the CV of the applicant and further collaboration between European laboratories. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteins Mots‑clés Bone mouse mechanical loading immunohistochemistry micro-array Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur UNIVERSITY OF BRISTOL Contribution nette de l'UE € 195 454,80 Adresse BEACON HOUSE QUEENS ROAD BS8 1QU Bristol Royaume-Uni Voir sur la carte Région South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 195 454,80