Appendicular skeletogenesis involves the development of both synovial joints and long bones. Alterations or absences in fetal movement and the resulting changes in mechanical stimulation are strongly implicated in a number of musculoskeletal clinical conditions which arise in utero, by disruption of specific processes critical to normal skeletogenesis: morphogenesis, the process of shape formation, cavitation, the separation of joint surfaces, and mineralisation, the transition of prenatal cartilage to bone. This doctorate explored the relationship between the role of movement and skeletal development.
The embryonic chick was immobilised for varying time periods, and the effect on hip joint morphogenesis and cavitation investigated. A defined time period of movement was found to be critical for normal hip joint morphogenesis and cavitation (Chapter 4). Applied in ovo external movements were then used to ‘rescue’ the effects of immobility on hip joint morphology and cavitation failure. A single, timed application of movement was found to ameliorate the effects of immobility on hip morphogenesis and cavitation (Chapter 5). Finally, a culture system was adapted in which in vitro prenatal murine forelimb and hind limb rudiments were subjected to controlled magnitudes of movements, in order to (1) explore the effects of dynamic loading on elbow and knee morphology and mineralisation compared to statically-cultured limbs, and (2) promote more normal morphogenesis and mineralisation in a muscleless mouse model of immobility. Dynamic loading led to an increase in joint outgrowth and shape complexity, and some increase in rudiment mineralisation, and also promoted more normal morphogenesis and mineralisation in the muscleless mutant (Chapter 6).
This research provides new insights into the role of movement on fetal skeletal development, and has advanced our understanding of how the timing of movement can alter the progression of joint shape, cavitation, or mineralisation. Knowledge of skeletal development is critical to developing strategies for early screening, diagnosis, prevention, and treatment of musculoskeletal abnormalities.