Novel therapeutics for bone growth disorders targeting the growth plate

PURPOSE AND AIM: Abnormal bone growth is a very common problem.

Many children with chronic diseases have impaired bone growth, others have leg length differences, or in rare cases extreme tall stature.

The purpose of this project is to develop new effective and safe therapeutic strategies for bone growth disorders by selectively targeting regulatory mechanisms in the growth plate.We seek to address three specific aims:To selectively modulate bone growth and growth plate fusion by selective estrogen receptor modulators.To explore the potential for humanin to prevent bone growth impairment caused by chronic disorders.To explore the potential for mechanical loading to locally stimulate bone growth.PROJECT ORGANISATION: The project leader will work 70% in the project and has overall responsibility for its progress.TIMEPLAN: This is a 5-year project including experimental and clinical studies.RESEARCH METHODS: We have established well-suited experimental models; human chondrocyte cell lines, organ cultures of human and rat growth plate tissues and genetically manipulated mice.

Equipment for applying mechanical load has been constructed.

A high-throughput screening approach of drug actions in the growth plate cartilage is in place.SIGNIFICANCE: We are uniquely positioned to detail regulatory mechanisms and actions of candidate drugs in the human growth plate.

Our preliminary data indicate that the project will lead to new treatment strategies for children with abnormal bone growth.