Novel therapeutic approach for the treatment of osteoporosis

1- Project title A novel therapeutic approach for the treatment of osteoporosis: Reducing Rspo3 could induce anabolic response and prevent bone loss 2- Content of research project This project is aimed at testing a novel therapeutic approach based on down-regulation of Rspo3 expression as a mean to prevent bone loss. This research project covers the background information related to bone loss (osteoporosis), the current available therapy approaches and their shortcomings, the hypothesis based on Rspo3 gene regulation as therapy and the experimental approach to prove this hypothesis. 3- Hypothesis The hypothesis of the proposed study is that decreasing Rspo3 will counter bone loss in an adult skeleton and that in an animal model of osteoporosis this approach will induce new bone formation and prevent bone loss. 4- Methods This study will include both in vitro and in vivo experiments. It will include all major molecular biology techniques like polymerase chain reaction (PCR), gel electrophoresis, expression cloning, gene expression arrays etc. The expertise of the host laboratory and my training during the PhD study will assure the successful completion of the proposed ambitious studies. 5- What is new and/or special about the project? Osteoporosisis a chronic condition characterized by loss of bone mass and deterioration of bone architecture. The main clinical presentation of the disease is fragility fractures that are associated with substantial pain and suffering, disability and even death for the affected patients and substantial costs to society. Therefore, there is an essential need to explore the molecular mechanisms that regulate bone homeostasis in the hope of identifying novel means to increase bone mass. The proposed study represents an entirely new paradigm that challenges the existing concept that inhibition of Rspos, upstream activators of the C-Wnt signaling, would decrease bone formation and bone mass. In contrast to this model, the host lab had found that partial deletion of Rspo3 (global deletion is lethal due to defects in placenta development) results in markedly increased bone formation and bone mass. In this proposed project, we will analyse whether by decreasing Rspo3 in an adult skeleton and in an animamodel of osteoporosis can induce new bone formation and prevent bone loss as a step to find new therapeutic mean for osteoporosis as well as in diseases where bone loss is the major clinical complication.