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Title: Mechanical stimulation and morphogenesis of the embryonic chick knee joint
Author: Chandaria, Vikesh
ISNI:       0000 0004 6421 2002
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Evolution has led to specialised shapes for each individual joint which are created during prenatal development through joint morphogenesis. Alterations or abnormalities in joint shape development can severely compromise joint function and have long-term health implications. Mechanical stimulation, due to fetal movements, plays an important role in the creation of joint shapes and a reduction in fetal movements has been highlighted as a risk factor for bone and joint shape malformation, which can lead to physical disability. This doctorate explored the relationship between mechanical stimulation and joint morphogenesis. A novel culture system was created in which embryonic chick hindlimb explants were subjected to controlled and quantified magnitudes of movements. The morphology of the knee joint from explants cultured under different mechanical conditions were compared to reveal how the magnitude of applied movement affects key aspects of the developing joint. A complex relationship was found between the magnitude of movement and the progression of joint shape development. This study provided evidence, for the first time, that the amount of movement experienced during development is a significant variable that impacts of the fate of prenatal joint development. Whilst dynamic movements were applied to developing joints, potential mechanotransduction pathways were tested for their involvement in modulating joint morphogenesis. Blocking the action of both stretch activated ion channels and voltage gated calcium channels produced joints shapes similar to those that had experienced no movement, suggesting the stimulating effects of dynamic movement were not acted upon. This research has provided a novel insight into how mechanical stimulation influences joint morphogenesis which is extremely valuable for understanding of the etiology of congenital joint conditions. Knowledge of how joints are first created is also valuable to the field of tissue engineering for developing treatments to regenerate degenerated joints.
Supervisor: Nowlan, Niamh Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral