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 by the osteoblast and bone resorption by the osteoclast. To gain insights into these complex mechanisms, we are studying the role of novel genes in osteoclast and osteoblast differentiation and activation. We have recently isolated the murine inositol phosphatase gene Inpp4b, which represents a novel negative regulator of osteoclast differentiation. Importantly, we showed that the human INPP4B is associated with bone mineral density and this gene can become a novel susceptibility factor for osteoporosis in the general healthy population. Because we found that Inpp4b is also expressed in osteoblast, Inpp4b role in osteoblast lineage will be investigated. Characterization of the cellular and molecular functions of Inpp4 will provide critical information on key steps of the intracellular signaling mechanisms in bone cells. These studies may lead to the discovery of novel prognostic risk factor and novel target genes translatable into design of therapeutic approaches for treatment of patients suffering from bone defects.