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The role of mechanical forces induced by prenatal movements in joint morphogenesis (MechJointMorph)
Date du début: 1 janv. 2014, Date de fin: 31 déc. 2018 PROJET  TERMINÉ 

Most joints start off the same during embryonic development, as two opposing cartilage surfaces, and are moulded into the diverse range of shapes seen in the adult in a process known as morphogenesis. While we understand very little of the biological or mechanobiological processes driving joint morphogenesis, there is evidence to suggest that fetal movements play a critical role in joint shape development. Developmental Dysplasia of the Hip (DDH), where the hip is partly or fully dislocated, is much more common when the baby’s movement is restricted or prevented. This proposal will determine how mechanical forces influence joint shape morphogenesis, which is of key relevance to neonatal joint conditions such as DDH, to adult joint health and disease, and to tissue engineering of cartilage. A mouse line in which mutant embryos have no skeletal muscle will be studied, providing the first in depth analysis of mammalian joint shape development for normal and abnormal mechanical environments. The mouse line could provide the first mammalian model system for prenatal onset DDH. ‘Passive’ movements of these mutant embryos will then be induced by massage of the mother, and the effects on the joints measured. If the effects on joint shape of absent spontaneous movement are mitigated by the treatment, this technique could eventually be used as a preventative treatment for DDH. Next, an in vitro approach will be used to quantify how much movement is needed for joint shape development. This research will provide an optimised protocol for applying biophysical stimuli to promote cartilage growth and morphogenesis in culture, providing valuable cues to cartilage tissue engineers. Finally, a computational simulation of joint shape morphogenesis will be created, which will integrate the new understanding gained from the experimental research in order to predict how different joints shapes develop in normal and abnormal mechanical environments.



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