Location and Contact Information
In all cultures, bone is viewed at best as a collection of inert calcified tubes and at worse as a symbol of death. This negative view is in flagrant contradiction with the survival purpose of all functions of bone. Indeed, bones protect internal organs in the case of trauma, confer the ability to hear, and to run. Hence, bones are needed to detect, protect of/or escape from an acute danger. In addition to these survival functions, bone is one of the latest tissues to appear during evolution. This means that it must use regulatory genes that are present only in bony vertebrates to orchestrate skeletogenesis during embryonic development and execute bone functions post-natally.
With this dual perspective in mind, our laboratory uses genetics, cellular, molecular and clinical physiological approaches to pursue several fundamental questions of bone biology. The first question that has been at the heart of the laboratory since its inception is to decipher all the molecular events leading to cell differentiation along the osteoblast (the bone-forming cell) lineage. The second line of research seeks to identify novel organs, hormones, and neurotransmitters that determine the ability of osteoblasts to make bone. A third line of research asks what is the cascade of molecular events that leads to bone-forming metastases such as the ones that prostate cancer, the most frequent cancer in males, forms in bone.
In the most recently established line of research in the laboratory, we are distancing ourselves from classical bone biology and instead are asking whether bone could have any other functions besides making bone? This latest line of research is based on the premise that we do not know the functions of all organs. This line of research has proven to be remarkably fruitful. It has revealed, for instance, that bone is an endocrine organ with a remarkably broad reach that affects physiological functions as diverse as memory, and the acute stress response, the ability to exercise, glucose metabolism and male fertility. The already large number of physiological functions regulated by bone in its endocrine capacity suggests a series of novel questions and hypotheses ideas that are all being investigated in the lab. Those are 1) Is this already large number of physiological functions regulated by bone an indication that more endocrine functions of bone are yet to be discovered? 2) For each of the endocrine functions of bone understudy, can we unravel their molecular bases? 3) Can we infer based on evolutionary or cellular consideration a coherence between the physiological functions regulated by bone? 4) Can we demonstrate a therapeutic relevance for any of the endocrine functions of bone in young or old animals? 5) Is there a specific cellular base for the endocrine functions of bone?
Current Lab Members
Julian Meyer Berger
Postdoctoral Research Scientist
Rogerio De Oliveira Batista
Postdoctoral Research Scientist
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.
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.
Berger JM, Singh P, Khrimian L, Morgan DA, Chowdhury S, Arteaga-Solis E, Horvath TL, Domingos AI, Marsland AL, Yadav VK, Rahmouni K, Gao XB and Karsenty G. Mediation of the acute stress response by the skeleton. Cell Met, In press, 2019