Objective We hypothesize that within the intervertebral disc (IVD), a niche exists comprising the nucleus pulposus and the inner layer of the annulus fibrosus and the cartilage endplate. In the niche, two events govern successful maintenance of disc cell function: the ability of progenitor cells to provide replacement cells, and the power of this cell population for renewal. In the disc niche, environmental conditions are unique in that the progenitor cells experience a low oxygen tension and possibly a low pH.Cellular adaptation to low oxygen (hypoxia) is an important biological problem not only in relation to pathological conditions such as cancer and ischemic diseases, but also in normal foetal development and in cell differentiation.The overall goal of this project is to investigate the role of hypoxia and HIFs transcription factors and the molecular mechanisms that are involved in the biology of IVD, especially in proliferation, survival, differentiation of NP cells and formation of NP tissue, in both developmental and degenerative processes.To achieve this aim, the proposed research activities will focus on: mice models of gene invalidation particularly regarding the HIF pathway (HIF-1α, HIF-2α and Von Hippel Lindau tumor suppressor protein). To specifically inactive these genes during embryonic development, growth or aging, conditional and inducible KO will be generated using Cre or Cre-ERT2 strategies and promoters for Foxa2 (notochordal cells) or aggrecan (NP cells).The expected results are to improve our understanding of IVD development, aging and associated pathologies. Such advances in the comprehension of IVD physiopathology may lead to the development of advanced approaches by defining novel therapeutic targets and/or innovative cell-based tissue engineering strategies. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologytissue engineeringmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Call for proposal FP7-PEOPLE-2011-IOF See other projects for this call Funding Scheme MC-IOF - International Outgoing Fellowships (IOF) Coordinator UNIVERSITE DE NANTES Address Quai de tourville 1 44035 Nantes cedex 1 France See on map Region Pays de la Loire Pays de la Loire Loire-Atlantique Activity type Higher or Secondary Education Establishments Administrative Contact Sébastien Davy (Mr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
