Patricia F. Ducy, PhD

Our research aims at defining the signaling network existing between the skeleton and other organs in the body using a combination of molecular and cell biology, mouse genetics, and physiological assays. Our main areas of interest include the crosstalk between pancreatic beta-cell biology and bone homeostasis, and the regulation of bone homeostasis by centrally controlled signals.

Bone is an expensive organ in terms of energy. A massive amount of proteins needs to be synthesized daily during bone growth, and during adulthood bones are constantly remodeled through a succession of destruction and formation that requires a remarkable supply of energy to bone cells. This demand is only magnified by the fact that the skeleton is one of the largest organs in the body. While a bony skeleton confers to vertebrate several survival advantages that justify this metabolic expense it also suggests that energy and bone metabolisms may regulate each other. Following this hypothesis we have identified osteocalcin as a bone-derived hormone regulating glucose metabolism and beta cell endowment. We have also have identified Gprc6a as the osteocalcin receptor in beta-cells and showed that osteocalcin/Gprc6a signaling regulates perinatal beta-cell proliferation. We are now testing whether a feed-forward loop between insulin production and osteocalcin secretion coordinates skeletogenesis and pancreas morphogenesis during development. We are also evaluating the role of osteocalcin during the beta-cells adaptation to pregnancy and are testing whether these cells declined proliferation and function during aging could be caused by decreased osteocalcin/Gprc6a signaling.

A second line of research in the lab is to evaluate the influence of brain-controlled signals on bone development, remodeling and osteocalcin secretion. Earlier studies have shown that brain serotonin negatively regulates the sympathetic tone, whose action on bone-forming osteoblasts via b2 adrenergic receptor signaling is deleterious for bone mass accrual. We used this observation to demonstrate that the deleterious effect of serotonin reuptake inhibitors (SSRIs) on bone health is caused by their stimulation of sympathetic output and could therefore by prevented by a co-treatment with a beta-blocker. We are now evaluating whether another brain-controlled molecule, melatonin, acts as a positive regulator of bone mass accrual by counteracting the negative effect of the sympathetic tone.