Grant: Operating Grant

The overall objective of our laboratory is to understand the molecular and cellular mechanisms that regulate bone homeostasis. Bone homeostasis requires equilibrium between bone formation and bone resorption by the osteoclast that derives from hematopoietic lineage. To gain insights into these complex mechanisms, we combine cellular and molecular approaches to characterize novel gene activities essential in osteoclast biology. We have recently isolated a novel lipid phosphatase, Inpp4b, associated with osteoclast differentiation/maturation and activation. To understand in vivo and ex vivo the role of this protein in osteoclast biology, we will use complementary approaches of specific inactivation/silencing as well as targeted expression of Inpp4b in the osteoclast. Importantly, based on our preliminary results, we will also investigate the role of INPP4B in human as a candidate gene for modulation of bone mineral density. These complementary experiments will provide us with a better understanding of the role of Inpp4b in osteoclast physiology. The characterization of the cellular and molecular functions of this protein in the osteoclast may lead to the discovery of novel target genes and the design of therapeutic approaches to be translated into a better treatment of patients suffering from bone defects.