Steven L. Teitelbaum, M.D.

Messing Professor
Pathology and Immunology

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-454-8463

  • 314-454-5078

  • 314-454-5505

  • 8118

  • BJC Institute of Health, 11th Floor, Suite 11106

  • teitelbs@wustl.edu

  • https://bonehealth.wustl.edu/research/laboratories/teitelbaum-lab/

  • bone biology, integrin biology, signal transduction, tumor necrosis factor, RANK ligand

  • Molecular mechanisms of osteoclast differentiation and bone resorption

Research Abstract:

The osteoclast is the unique resorptive cell of the skeleton and its relative hyperactivity is responsible for all forms of pathological bone loss, such as osteoporosis. Our laboratory focuses on the mechanisms by which the osteoclast resorbs bone with the goal of identifying new molecular targets for preventing and treating pathological bone loss. In recent years we have turned our attention to the osteoclast cytoskeleton whose organization and polarization are fundamental to the resorptive process. Our strategy is to first characterize the phenotype mice lacking the gene encoding the protein of interest. If a robust phenotype is uncovered, we generate pure populations of osteoclasts bearing the relative genotypes in culture and explore their function by molecular and cell biological means. Doing so, we have established that the osteoclast organizes its cytoskeleton in an αvβ3 integrin-dependent manner and have detailed a canonical signaling pathway by which the cell accomplishes its goal. We have also determined the interplay between this system and osteoclast-essential cytokines such as M-CSF and RANK ligand. Recently we have made the surprising discovery that autophagy-related proteins also regulate the capacity of the osteoclast to polarize and resorb bone. Given the tools we have in hand, our trainees have been central to taking the cell apart.

Selected Publications:

Warren, J.T., Nelson, C.A., Decker, C.E., Zou, W., Fremont, D., Teitelbaum, S.L.. Manipulation of Receptor Oligomerization as a Novel Strategy for TNF Superfamily Inhibition. Sci Signal 2014 [Epub ahead of print]

Fukunaga, T., Zou, W., Warren, J.T., Teitelbaum, S.L. Vinculin regulates osteoclast function. J Biol Chem 289(19):13554-64, 2014

Zou, W., Monkley, S.J., Critchley, D.R., Petrich, B.G., Ginsberg, M.H., Teitelbaum, S.L. Talin1 and Rap1 are critical for osteoclast function. Mol Cell Biol 33:830-844, 2013.

Izawa, T., Zou, W., Chappel, J.C., Ashley, J.W., Feng, X., Teitelbaum, S.L. c-Src Links a RANK/αvβ3 Integrin Complex to the Osteoclast Cytoskeleton. Mol Cell Biol 32:2943-2953, 2012.

Croke, M., Ross, F.P., Korhonen, M., Williams, D.A., Zou, W., Teitelbaum, S.L. Rac deletion in osteoclasts causes severe osteopetrosis. J Cell Sci 124:3811-3821, 2011.

DeSelm, C.J., Miller, B.C., Zou, W., Beatty, W.L., van Meel, E., Takahata, Y., Klumperman, J., Tooze, S.A., Teitelbaum, S.L., Virgin, H.W. Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev Cell. 21:966-74, 2011. Co-corresponding author.

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.

Last Updated: 8/6/2014 10:31:24 AM

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