Location and Contact Information
Our laboratory studies all aspects of skeletal biology. The skeleton is made of two tissues, cartilage and bone and three main cell types chondrocyte in cartilage, osteoblast, and osteoclast in bone. Chondrocyte and osteoblast are of mesenchymal origin whereas osteoclasts derive from the myelomonocytic lineage.
In terms of developmental biology, we have identified transcription factors (“master genes”) that control positively or negatively the entire cascade of differentiation of mesenchymal cells into osteoblasts. We have expanded this work to chondrocyte as well as to differentiation of cells of the parathyroid gland, an endocrine gland that plays a major role during bone remodeling. We have also identified microRNAs that modulate the activity of Runx2, the master transcription factor of osteoblast differentiation.
In terms of physiology which is currently the main interest of the lab, we have pursued two distinct questions. The first one is to provide a molecular genetics explanation for known functions of the skeleton, the regulation of which was poorly understood. In doing so, we have, for instance, provided a genetic explanation for why mineralization of the extracellular matrix occurs only in bone, as well as for pathological calcification. We have also shown that bone mass accrual is under the control of the brain and provided a road map of the endocrine and neuronal circuitry implicated in the central regulation of bone mass.
More recently our laboratory has asked another question: Does the skeleton have any other functions than making bone? In addressing this question we have identified osteocalcin as a bone-derived hormone that is necessary and sufficient to promote multiple physiological functions that are all characterized by the fact they decline early in life and are needed for survival in a hostile environment. Those include but are not limited to male fertility, memory, adaptation to exercise, energy expenditure, insulin secretion and glucose homeostasis and aspects of the stress response. Our goals are to decipher the molecular bases of these functions and to demonstrate that the endocrine function of bone, explains why many physiological functions are regulated differently in bony vertebrates than in other animals. To address these challenges we use mouse genetics, molecular and cellular biology approaches as well as physiological assays. Current projects in the lab include:
- Unraveling the molecular bases of bone metastasis from prostate cancer.
- Defining the role of osteocalcin in energy metabolism.
- Defining the role of osteocalcin in the central and peripheral nervous system.
- Demonstrating the implication of the dysregulation of osteocalcin in the pathogenesis of human diseases.
- Identifying regulators of the secretion of osteocalcin.
Current Lab Members
Postdoctoral Research Fellow
Julian Meyer Berger
Student, Graduate School of Arts and Sciences
Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galan-Diez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, Bacchetta J, Szulc P, Kitsis RN, de Cabo R, Friedman RA, Torsitano C, McGraw TE, Puchowicz M, Kurland I and Karsenty G. Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 2016 23 (6):1078-92.
Wei J, Shimazu J, Makinistoglu M, Maurizi A, Kajimura D, Zong H, Takarada T, Iezaki T, Pessin JE, Hinoi E, and Karsenty G. Glucose uptake and Runx2 synergize to orchestrate osteoblast differentiation and bone formation. Cell. 2015 161 (7): 1576-91.
Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013 Sep 26;155(1):228-41. doi: 10.1016/j.cell.2013.08.042.
Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G. Endocrine regulation of male fertility by the skeleton. Cell. 2011 Mar 4;144(5):796-809. doi: 10.1016/j.cell.2011.02.004. Epub 2011 Feb 17.
Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010 Jul 23;142(2):296-308. doi:10.1016/j.cell.2010.06.003.
Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007 Aug 10;130(3):456-69.