Biomedical Research Education & Training
Faculty Member

Elefteriou, Florent, Ph.D.
Adjunct Associate Professor of Medicine

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Phone Number: 615-322-7975

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Elefteriou, Florent's picture
Academic history
PhD, Universite Claude Bernard

Office Address   Mailing Address

MRB IV, Light Hall, room 1235H

1235 MRB IV 0575

Research Keywords
bone, osteoblast, osteoclast, bone remodeling, leptin, adrenergic receptor, norepinephrine transporter, neurofibromatosis, NF1, skeletal dysplasia, dwarfism, cancer metastasis,Cancer,Developmental biology,Endocrinology,Gene regulation,Genetics,Knockout,Malignancy,Molecular medicine,Mouse,Neuroscience,Pharmacology,Physiology,Receptor,Signal transduction

Research Description
Bone remodeling is regulated in vivo by a complex interplay between autocrine/paracrine and hormonal signals. Our studies, based on the use of mouse genetic models, demonstrated that this process is also regulated by the central nervous system, and that, as this finding implies, bone remodeling is an homeostatic process fully integrated to the regulation of the internal milieu via neurons, neuropeptides and hormones involved in the regulation of body weight, energy expenditure, reproduction or immunity. Our studies also identified the sympathetic nervous system as a critical regulator of bone remodeling. Our research currently focuses on the clinical implications of these findings from preclinical mouse models, with a special interest on osteoporosis and bone cancer metastasis.

The second main interest of our laboratory is to determine the role of Nf1 in bone cells and type I neurofibromatosis (NF1). Neurofibromatosis, caused by mutations in the Nf1 gene, is characterized by several skeletal complications including macrocephaly, scoliosis, bowing of the tibia and pseudo-arthrosis, but the origin of these skeletal dysplastic defects is unknown. By the use of mutant mouse models lacking Nf1 in osteoblasts, chondrocytes or mesenchymal stem cells, we are currently investigating the role of Nf1 signaling in the differentiation and function of bone cells, with the goal of identifying novel signaling pathways and transcription factors regulating bone growth, remodeling and repair, and to identify new therapeutic targets to treat bone diseases, including skeletal displasiae and fracture non-unions found in NF1 patients.

Campbell, JP, Karolak, MR, Ma, Y, Perrien, DS, Masood-Campbell, SK, Penner, NL, Munoz, SA, Zijlstra, A, Yang, X, Sterling, JA, Elefteriou, F. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. PLoS Biol, 10(7), e1001363, 2012

Campbell, JP, Merkel, AR, Masood-Campbell, SK, Elefteriou, F, Sterling, JA. Models of bone metastasis. J Vis Exp(67), e4260, 2012

Edwards, JR, Perrien, DS, Fleming, N, Nyman, JS, Ono, K, Connelly, L, Moore, MM, Lwin, ST, Yull, FE, Mundy, GR, Elefteriou, F. Silent information regulator (Sir)T1 inhibits NF??B signaling to maintain normal skeletal remodeling. J Bone Miner Res, 2012

Wang, W, Lian, N, Ma, Y, Li, L, Gallant, RC, Elefteriou, F, Yang, X. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Development, 139(3), 601-11, 2012

Elefteriou, F, Yang, X. Genetic mouse models for bone studies--strengths and limitations. Bone, 49(6), 1242-54, 2011 PMCID:3331798

Ma, Y, Nyman, JS, Tao, H, Moss, HH, Yang, X, Elefteriou, F. I?2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Endocrinology, 152(4), 1412-22, 2011 PMCID:3060633

Wang, W, Nyman, JS, Ono, K, Stevenson, DA, Yang, X, Elefteriou, F. Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I. Hum Mol Genet, 20(20), 3910-24, 2011 PMCID:3331798

Wang, W, Nyman, JS, Moss, HE, Gutierrez, G, Mundy, GR, Yang, X, Elefteriou, F. Local low-dose lovastatin delivery improves the bone-healing defect caused by Nf1 loss of function in osteoblasts. J Bone Miner Res, 25(7), 1658-67, 2010

Elefteriou, F, Kolanczyk, M, Schindeler, A, Viskochil, DH, Hock, JM, Schorry, EK, Crawford, AH, Friedman, JM, Little, D, Peltonen, J, Carey, JC, Feldman, D, Yu, X, Armstrong, L, Birch, P, Kendler, DL, Mundlos, S, Yang, FC, Agiostratidou, G, Hunter-Schaedle, K, Stevenson, DA. Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am J Med Genet A, 149A(10), 2327-38, 2009

Lian, N, Wang, W, Li, L, Elefteriou, F, Yang, X. Vimentin inhibits ATF4-mediated osteocalcin transcription and osteoblast differentiation. J Biol Chem, 2009

Wang, W, Lian, N, Li, L, Moss, HE, Wang, W, Perrien, DS, Elefteriou, F, Yang, X. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription. Development, 136(24), 4143-53, 2009

Elefteriou, F. Regulation of bone remodeling by the central and peripheral nervous system. Arch Biochem Biophys, 473(2), 231-6, 2008 PMCID:2430105

Singh, MK, Elefteriou, F, Karsenty, G. Cocaine and amphetamine-regulated transcript may regulate bone remodeling as a circulating molecule. Endocrinology, 149(8), 3933-41, 2008 PMCID:2488246

Patel, MS, Elefteriou, F. The New Field of Neuroskeletal Biology. Calcif Tissue Int, 2007

Elefteriou, F, Benson, MD, Sowa, H, Starbuck, M, Liu, X, Ron, D, Parada, LF, Karsenty, G. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab, 4(6), 441-51, 2006 PMCID:2756713

Mundy, GR, Elefteriou, F. Boning up on ephrin signaling. Cell, 126(3), 441-3, 2006

Elefteriou, F. Neuronal signaling and the regulation of bone remodeling. Cell Mol Life Sci, 62(19-20), 2339-49, 2005

Elefteriou, F, Ahn, JD, Takeda, S, Starbuck, M, Yang, X, Liu, X, Kondo, H, Richards, WG, Bannon, TW, Noda, M, Clement, K, Vaisse, C, Karsenty, G. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature, 434(7032), 514-20, 2005

Cock, TA, Back, J, Elefteriou, F, Karsenty, G, Kastner, P, Chan, S, Auwerx, J. Enhanced bone formation in lipodystrophic PPARgamma(hyp/hyp) mice relocates haematopoiesis to the spleen. EMBO Rep, 5(10), 1007-12, 2004 PMCID:1299154

Cui, Y, Huang, L, Elefteriou, F, Yang, G, Shelton, JM, Giles, JE, Oz, OK, Pourbahrami, T, Lu, CY, Richardson, JA, Karsenty, G, Li, C. Essential role of STAT3 in body weight and glucose homeostasis. Mol Cell Biol, 24(1), 258-69, 2004 PMCID:303343

Elefteriou, F, Karsenty, G. [Bone mass regulation by leptin: a hypothalamic control of bone formation. Pathol Biol (Paris), 52(3), 148-53, 2004

Elefteriou, F, Takeda, S, Ebihara, K, Magre, J, Patano, N, Kim, CA, Ogawa, Y, Liu, X, Ware, SM, Craigen, WJ, Robert, JJ, Vinson, C, Nakao, K, Capeau, J, Karsenty, G. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci U S A, 101(9), 3258-63, 2004 PMCID:365777

Elefteriou, F, Ducy, P. [Control of body mass by leptin occurs through the sympathetic nervous system. Med Sci (Paris), 19(4), 391-3, 2003

Elefteriou, F, Takeda, S, Liu, X, Armstrong, D, Karsenty, G. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass. Endocrinology, 144(9), 3842-7, 2003

Levasseur, R, Barrios, R, Elefteriou, F, Glass, DA, Lieberman, MW, Karsenty, G. Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice. Endocrinology, 144(7), 2761-4, 2003

Takeda, S, Elefteriou, F, Karsenty, G. Common endocrine control of body weight, reproduction, and bone mass. Annu Rev Nutr, 23, 403-11, 2003

Takeda, S, Elefteriou, F, Levasseur, R, Liu, X, Zhao, L, Parker, KL, Armstrong, D, Ducy, P, Karsenty, G. Leptin regulates bone formation via the sympathetic nervous system. Cell, 111(3), 305-17, 2002

Elefteriou, F, Exposito, JY, Garrone, R, Lethias, C. Binding of tenascin-X to decorin. FEBS Lett, 495(1-2), 44-7, 2001

Lethias, C, Elefteriou, F, Parsiegla, G, Exposito, JY, Garrone, R. Identification and characterization of a conformational heparin-binding site involving two fibronectin type III modules of bovine tenascin-X. J Biol Chem, 276(19), 16432-8, 2001

Elefteriou, F, Exposito, JY, Garrone, R, Lethias, C. Cell adhesion to tenascin-X mapping of cell adhesion sites and identification of integrin receptors. Eur J Biochem, 263(3), 840-8, 1999

Elefteriou, F, Exposito, JY, Garrone, R, Lethias, C. Characterization of the bovine tenascin-X. J Biol Chem, 272(36), 22866-74, 1997

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