Research Faculty

650 West 168th Street
Black Building BB-1412
New York, NY 10032

Phone: 212-305-9299
Patricia F. Ducy, Ph.D.
Associate Professor of Pathology & Cell Biology at CUMC
Research Summary

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 2 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.
Selected Publications

Ortuno MJ, Robinson ST, Subramanyam P, Paone R, Huang YY, Guo XE, Colecraft HM, Mann JJ, Ducy P. Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat Med. 22:1170-79 (2016).

Wei J, Hanna T, Suda N, Karsenty G, Ducy P. Osteocalcin promotes β-cell proliferation during development and adulthood through Gprc6a. Diabetes 63:1021-31 (2014).

Inose H, Zhou B, Yadav VK, Guo XE, Karsenty G, Ducy P. Efficacy of serotonin inhibition in mouse models of bone loss. J Bone Miner. Res. 26:2002-11 (2011).

Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat. Med. 16:308-312 (2010).

Yadav VK, Arantes HP, Barros ER, Lazaretti M, Ducy P. Genetic Analysis of Lrp5 Function in Osteoblast Progenitors. Calcif. Tissue Int. 86: 382-388 (2010).

Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates -cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc. Natl. Acad. Sci. USA. 105:5266-70 (2008).

Yadav VK, Ryu J-H, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum: an entero-bone endocrine axis. Cell 135:825-37 (2008).

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