Grant: Operating Grant

Our ultimate goal is to understand the molecular and cellular mechanisms that regulate bone homeostasis. Throughout life, equilibrium between two opposite phenomena, bone formation and bone resorption, has to be maintained. Specific cells, osteoblast and osteoclast are responsible respectively for bone tissue synthesis and degradation. The osteoclast is from hematopoietic origin and when its activity is lost, severe diseases as osteoporosis and osteopetrosis can occur. Particularly, osteopetrosis is observed when osteoclast cells are deficient or absent, thereby causing an excess of bone mass and a poorly developed bone marrow cavity, leading to death. To gain insights into osteopetrosis, we are studying a mouse model of this disease called grey-lethal (gl) that reproduces the human infantile and most severe form of this disorder. We recently isolated and characterized the gene responsible for this disease using a positional cloning approach. We have now entered a new phase of our studies that consists in the characterization of the grey-lethal gene function and its normal biological role in bone homeostasis and hematopoiesis at large. In addition, we will investigate into the intracellular function of gl in the osteoclast activation pathway. The characterization of this osteopetrotic gene is fundamental for the future development of potential therapeutic strategies.