Periodic Reporting for period 1 - BONE-JOINT-MORPH (Mechanobiology of Proprioceptive Regulation of Bone and Joint Morphogenesis)
Période du rapport: 2018-09-01 au 2020-08-31
Physiological movement, including movement before birth (fetal movement), is necessary for maintaining a proper mechanical environment which will facilitate musculoskeletal development. Developmental dysplasia of the hip (DDH) is a condition which can result due to abnormal loading either before or after birth. With DDH, the acetabular socket is often shallow causing an improper fit of the femoral head within the socket, leading to hip instability or even dislocation6. DDH is the most commonly abnormal joint in new-born babies, with an incidence of 4.9 out of 100012. However, it is not known why the hip, more than any other joint in the body, is so dependent on movements and mechanical stimulation for its normal development. Recent studies on the proprioceptive system (the neuromuscular sensory receptors responsible for registering position and movement of body parts) have indicated a key role in skeletogenesis. Disruption of the proprioceptive system in mice through knocking out Runt-related transcription factor 3 (RUNX3 KO has been found to cause gait ataxia, spinal scoliosis and fracture misalignment. Excitingly, unpublished data from the same animal model has indicated that hip dysplasia consistently occurs in these mice (Fig. 1), with all other synovial joints forming normally. It is hypothesised that the hip joint abnormalities arise as a direct effect of the abnormal mechanical environment due to abnormal gait. Therefore, this model system offers a unique opportunity to reveal how movement shapes the developing joint, and in particular, why the hip joint is more dependent on normal movements than any other joint. Therefore, this project will potentially reveal new insights into the causes and aetiology of DDH.
The musculoskeletal modelling framework was established.
The walkway for mouse gait recording was designed and developed.
The protocol to record the gait of the healthy and mutant mouse was established.
The walkway for mouse gait recording was designed and developed.
The protocol to record the gait of the healthy and mutant mouse was established.
The project was terminated before the scheduled end date as I received a permanent job in academia elsewhere. However, I am still in touch with my mentors and we are planning to take the project forward through suitable external funding.