Understanding Bone Unloading and Loading and Healing Responses

Summary

Osteoporosis and fracture care are currently important topics for society at large. Osteoporosis not only happens to the aged, but also in children with or without various bone disorders. Some of these children also have difficulties in bone healing. Biomechanics and bone loading is important for bone maintenance and local osteopenia associated with bone unloading can negatively affect bone repair. A greater understanding of the genetic pathways involved with bone loading will allow for development of new intervention strategies to improve patient outcomes.

Supervisor(s)

Professor David Little, Dr Aaron Schindeler

Research Location

Westmead - Children's Hospital at Westmead Clinical School

Program Type

PHD

Synopsis

Recent advances in understanding the Wnt pathway have led to the important roles of two secreted proteins, Sclerostin (SOST) and Dickkopf1 (Dkk1). Our laboratory has specific expertise and access to unique reagents in this area. We have access to knockout mice and our own colony of Dkk1 null mice. Both these strains have increased bone formation leading to robust bones. By analysing the responses of these mice to unloading, which normally causes localised osteoporosis, we can begin to untangle the role of and DKK1 in this process. It is already known that SOST and DKK1 are intricately involved in the transduction of mechanosensory signals in bone. The specific task of the student will be to characterise a BOTOX induced paralysis model of osteopenia, in terms of bone density and changes in trabecular architecture. On site bone density and MicroCT scanning is available in our laboratory. The roles of SOST and DKK1 in unloading osteopenia and load induced bone formation will be analysed by expression profiles in wild type mice, and characterisation of altered responses in mutant mice. Prevention of osteopenia by application of therapeutics aimed at DKK1 and will also be explored. Fracture healing is also advanced in these robust mice and also with treatments aimed at blocking SOST and DKK1. Experiments on osteoporotic fracture healing and various other models are being explored with these reagents.

Additional Information

Techniques used include cell culture, transgenic/knockout mouse analysis, molecular biology, DEXA and MicroCT imaging, Histology and Immunohistochemistry. PhD scholarships top-ups available to be judged based on the strength of the applicant.

Keywords

Orthopaedics, Paediatrics, Bone healing, Fractures, Bone development, Bone cell biology, Cell biology, Movement, Genes in biology & medicine, cell culture, Genetic mouse models, Cre-Lox recombination, Flow cytometry

Opportunity ID

The opportunity ID for this research opportunity is: 1263

Other opportunities with Professor David Little

• The cellular determinants of bone repair
• Chondrocyte to osteoblastic conversion in bone development and repair

Other opportunities with Dr Aaron Schindeler

• Chondrocyte to osteoblastic conversion in bone development and repair
• The cellular determinants of bone repair