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Faculty > Faculty Alphabetical > Steven Teitelbaum, MD

Messing Professor, Pathology and Immunology
Acting Head, Anatomic and Molecular Pathology
Prefessor, Medicine
Room 2469, Barnes-Jewish Hospital North
Office: (314) 454-8463
Lab: (314) 454-5078
E-mail: teitelbs@wustl.edu
Web-site: http://pathology.wustl.edu/~teitelbaumlab
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Research

Skeletal mass is the product of the activities of two cell types: osteoclasts which resorb bone and osteoblasts which synthesize it. The focus of our laboratory is to delineate the means by which osteoclasts and osteoblasts differentiate and function at the cellular and molecular levels and use this information to understand the pathogenesis of osteoporosis. The projects ongoing in our laboratory include:

1) The role of v-associated integrins in osteoclastic bone resorption. We find the integrin v3 essential to the resorptive process. We have cloned the 3 integrin cDNAs, and its promoter and have detailed the relevant regulatory mechanisms. This effort has permitted us to pharmacologically prevent osteoporosis by v3 antagonists and generate a 3 knockout mouse with as striking bone phenotype. Using this mouse, we have identified the components of the 3 integrin cytoplasmic domain which regulate osteoclast function and have defined the intracellular signals transmitted by the integrin which activate the cell.

2) The role of TNF in osteoclast regulation. We have shown TNF is a potent bone resorptive agent responsible for inflammatory osteolysis exerting its effect via the p55 TNF receptor. These studies involve various strains of knockout mice lacking TNF isoforms or specific receptors. We also find, using a novel chimeric mouse generated in our laboratory, that TNF-induced osteoclast formation reflects direct targeting of the cytokine to osteoclast precursors, an event requiring constitutive levels of RANK ligand, a TNF family member essential for osteoclast development. Our present studies focus on the interplay of inflammatory cytokines in the pathogenesis of the bone loss of rhematoid arthritis.

Editorial Responsibilities

PresentEditorial BoardJournal of Bone and Mineral Research
PresentEditorial BoardJournal of Cellular Biochemistry
PresentEditorial BoardJournal of Bone and Joint Surgery
PresentEditorial BoardBone
PresentEditorial BoardJournal of Regenerative Medicine

DBBS Graduate Program Affiliation

Molecular cell biology program

Diagnostic Expertise

Metabolic diseases of bone

Clinical Interest

Anatomic and Molecular Pathology - Non-neoplastic Bone Pathology

Selected Publications

Feng Y, Zhao H, Luderer HF, Epple H, Faccio R, Ross FP, Teitelbaum SL, Longmore GD. The LIM protein, Limd1, regulates AP-1 activation through an interaction with Traf6 to influence osteoclast development. J Biol Chem. 2007 Jan 5;282(1):39-48. Epub 2006 Nov 8, 2007 Abstract

Feng Y, Zhao H, Luderer H, Epple H, Faccio R, Ross FP, Teitelbaum SL, Longmore GD. The LIM protein, LIMD1, regulates AP-1 activation through an interaction with TRAF6 to influence osteoclast development. J Biol Chem. 2007 Jan 5;282:39-48, 2007 Abstract

Kitaura, H., Zhou, P., Novack, D.V., Ross, F.P., Teitelbaum, S.L. M-CSF mediates TNF-induced inflammatory osteolysis. J Clin Invest 115:3418-3427, 2005 Abstract

Ross, F.P., Teitelbaum, S.L. alphavbeta3 and M-CSF; partners in osteoclast biology. Immunological Reviews 208:88-105, 2005 Abstract

Bai, S., Kitaura, H., Zhao, H., Chen, J., Mueller, J.M., Schuele, R., Darnay, B., Novack, D.V., Ross. FHL2 inhibits the osteoclast in a TRAF6 dependent manner. J Clin Invest 115:2742-2751, 2005 Abstract

Faccio, R., Teitelbaum, S.L., Fujikawa, K., Chappel, J., Zallone, A., Tybulewicz, V.L., Ross, F.P.,. Vav3 regulates osteoclast function and bone mass. Nat Med 11:284-290, 2005 Abstract

Zhao, H., Ross, F.P., Teitelbaum, S.L. Unoccupied pvr3 integrin regulates osteoclast apoptosis by transmitting a positive death signal. Molec Endocrinol 19:771-780, 2005 Abstract

Wei, S., Kitaura, H., Zhou, P., Ross, F.P., Teitelbaum, S.L. Interleukin-1 mediates tumor necrosis factor-induced osteoclastogenesis. J Clin Invest 115:282-290, 2005 Abstract

Kitaura, H., Sands, M.S., Aya, K., Zhou, P., Hirayama, T., Uthgenannt, B., Wei, S., Takeshita, S., S. Marrow stromal cells and osteoclast precursors differentially contribute to TNF-p induced osteoclastogenesis in vivo. J Immunol 173:4838-4846, 2004 Abstract

Teitelbaum, S.L. RANKing c-Jun in osteoclast development. J Clin Invest 114:463-5, 2004 Abstract

Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638-649, 2003 Abstract

Faccio R, Takeshita S, Zallone A, Ross FP, Teitelbaum SL. c-Fms and the v3 integrin collaborate during osteoclast differentiation. J Clin Invest 111:749-758, 2003 Abstract

Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL. The I kappa B function of NF-kappa b2 p100 controls stimluated osteoclastogenesis. J Exp Med 198:771-781, 2003 Abstract

Faccio R, Novack DV, Zallone A, Ross FP, Teitelbaum SL. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta 3 integrin. J Cell Biol 162:499-509, 2003 Abstract

Faccio R, Takeshita S, Zallone A, Ross FP, Teitelbaum SL. Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638-649, 2003 Abstract

Takeshita S, Namba N, Zhao JJ, Jiang Y, Genant HK, Silva MJ, Brodt MD, Helgason CD, Humphries RK, Kr. Ship deficient mice are severely osteoporotic due to accelerated bone resorption by pagetic-like osteoclasts. Nat Med 8:943-949, 2002 Abstract

Wei S, Wang MW, Teitelbaum SL, Ross FP. Interleukin-4 reversibly inhibits osteoclastgenesis via inhibition of NF-kB and MAP kinase signaling. J Biol Chem 277:6622-6630, 2002 Abstract

Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J Clin Invest 108:971-979, 2001 Abstract

Abu-Amer Y, Dowdy SF, Ross FP, Clohisy JC, Teitelbaum SL. TAT Fusion Proteins Containing Tyrosine 42-deleted IkBa Arrest Osteoclastogenesis. J Biol Chem 276:30499-30503, 2001 Abstract

Feng X, Novack DV, Faccio R, Ory DS, Aya K, Boyer MI, McHugh KP, Ross FP, Teitelbaum SL. A Glanzmanns Mutation of the 3 Integrin Gene Specifically Impairs Osteoclast Function. J Clin Invest 107:1137-1144, 2001 Abstract

Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL. TNF--induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of rank ligand. J Clin Invest 106:1481-1488, 2000 Abstract

Teitelbaum SL. Bone resorption by osteoclasts. Science 289:1504-1508, 2000 Abstract

Abu-Amer Y, Erdmann J, Kollias G, Ross FP, Teitelbaum SL. Tumor necrosis factor receptors types 1 and 2 differentially regulate osteoclastogenesis. J Biol Chem 275:27307-27310, 2000 Abstract

McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, Novack D, Feng X, Ross FP, Hynes RO, Teitelba. Mice lacking 3 integrins are osteosclerotic due to dysfunctional osteoclasts. J Clin Invest 105:433-440, 2000 Abstract


Current Trainees

Yuji Ito, MD
Kazuhiro Kanaoka, PhD
Jikun Zha, PhD
Ping Zhou, PhD
Shuting Bai, MD, PhD
Hyun-Ju Kim, PhD

Past Trainees

Haibo Zhao, MD, PhD
Research Associates
Wei Zou