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Steven Teitelbaum, MD

Wilma and Roswell Messing Professor of Medicine, Pathology and Immunology

Phone314-454-8463

Fax314-454-5505

Emailteitelbs@wustl.edu

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Recognition

President, American Society for Bone and Mineral Research, 1992-93
American Society for Bone and Mineral Research, William F. Newman Award, given for outstanding and major scientific contributions in the area of bone and mineral research and for contributions to associates and trainees in teaching, research and administration, 1998
President, FASEB, 2002 – 2003
Boy Frame Award for Clinical Excellence in the Field of Bone and Mineral Metabolism, American Society for Bone and Mineral Research, 2003
Rous-Whipple Award, American Society for Investigative Pathology, 2006
MERIT Award, National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2010

Clinical Interests

Metabolic Diseases of Bone
Osteoporosis
Renal Osteodystrophy

Research Interests

Our laboratory focuses on the mechanisms by which osteoclasts resorb bone. Our general strategy is to establish that deletion of a molecule of interest, in vivo, produces a robust skeletal phenotype. If we find such is the case, we employ molecular and cellular techniques to determine the mechanisms by which the targeted molecule regulates the osteoclast and potential clinical relevance. We have established that organization of the osteoclast’s unique cytoskeleton, which is central to its capacity to resorb bone, is mediated by an αvβ3 integrin-activated signaling complex involving c-Src, Syk, Dap12, Slp76, Vav3 and Rac. We have proven the physiological relevance of each of these signaling molecules as their deletion results in osteoclast dysfunction and osteopetrosis, in vivo. Deletion of these molecules is also protective of pathological bone loss and thus, they are candidate therapeutic targets. We have established that the osteoclastogenic cytokines, M-CSF and RANK ligand, regulate the osteoclast cytoskeleton by stimulating the same signals as the αvβ3 integrin. In the case of M-CSF, its collaboration with the integrin represents inside-out conformational stimulation mediated by talin. RANK ligand, on the other hand, requires αvβ3 for its cytoskeletal effects, but by different mechanisms which are presently under investigation. Finally, we have established that the osteoclast exerts its bone resorptive effects by functioning as a secretory cell wherein lysosomal vesicles containing skeleton-degrading molecules polarize and insert into the bone-apposed plasma membrane under the influence of Synaptotagmin VII and autophagy proteins. The polarized resorptive machinery thereby creates an isolated extracellular microenvironment in which bone is degraded.

Publications

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.
Kim, H.J., Zhao, H., Kitaura, H., Bhattacharyya, S., Brewer, J.A., Muglia, L.J., Ross, F.P., Teitelbaum, S.L. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116:2152-60, 2006.
Zou, W., Kitaura, H., Reeve, J., Tybulewicz, V.L.J., Shattil, S.J., Ginsberg, M.H., Ross, F.P., Teitelbaum, S.L. Syk, c-Src and the v3 integrin, in concert, regulate osteoclastic bone resorption. J Cell Biol 176:877-888, 2007.
Zhao, H., Chappel, J., Ito, Y., Andrews, N.W., Teitelbaum, S.L., Ross, F.P. Synaptotagmin VII regulates bone remodeling by modulating osteoclast and osteoblast secretion. Dev Cell 14:914-925, 2008.
Zou, W., Zhu, T., Craft, S.S., Broekelmann, T.J., Mecham, R.P., Teitelbaum, S.L. Cytoskeletal dysfunction dominates in Dap12-deficient osteoclasts. J Cell Sci 123:2955-2963, 2010.

Editorial Responsibilities

Advisory Editorial Board: Journal of Experimental Medicine
Editorial Board: Cell Metabolism

DBBS Graduate Program Affiliation

Molecular Cell Biology

Professional Societies and Organizations

  • American Society for Clinical Investigation
  • Association of American Physicians
  • American Society for Bone and Mineral Research
  • International Bone and Mineral Society
  • American Society for Investigative Pathology