help button home button Endocrine Society Molecular Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on December 9, 2004
Molecular Endocrinology, doi:10.1210/me.2004-0161
A more recent version of this article appeared on March 1, 2005
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
19/3/771    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, H.
Right arrow Articles by Teitelbaum, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, H.
Right arrow Articles by Teitelbaum, S. L.

Submitted on April 16, 2004
Accepted on November 29, 2004

Unoccupied {alpha}v{beta}3 Integrin Regulates Osteoclast Apoptosis by Transmitting a Positive Death Signal

Haibo Zhao, F. Patrick Ross, and Steven L. Teitelbaum*

Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 S. Euclid, St. Louis, Missouri 63110

* To whom correspondence should be addressed. E-mail: teitelbs{at}wustl.edu.

Cell/matrix detachment is a general inducer of programmed cell death, an event mediated by loss of integrin/ligand association. Because {alpha}v{beta}3 is the major integrin expressed by the osteoclast, we asked if its occupancy promotes survival of the resorptive cell. Thus, we generated wild type pre-osteoclasts and placed them on selective matrix proteins. Consistent with the posture that {alpha}v{beta}3 occupancy promotes survival, pre-osteoclasts plated on native collagen, a matrix not recognized by the integrin, undergo apoptosis four fold faster than those on the {alpha}v{beta}3 ligand, vitronectin. To further explore the role of {alpha}v{beta}3 in osteoclast apoptosis, wild type and {beta}3-/- pre-osteoclasts were suspended and apoptosis determined, with time. {beta}3-/- pre-osteoclasts, in suspension, undergo a rate of apoptosis only 40-60% of that of their wild type counterparts indicating that unoccupied {alpha}v{beta}3 transmits a positive death signal which we find regulated by caspase-8. Attesting to specificity of the unoccupied integrin-transmitted death signal, apoptosis in the absence of {alpha}v{beta}3 is mediated by capsase-9. We have shown that the resorptive defect of {beta}3-/- osteoclasts is rescued by wild type {beta}3 cDNA but not one bearing a S752P mutation. To determine if the same holds as regards osteoclast apoptosis, we constructed lentivirus vectors encoding GFP, wild type {beta}3 or {beta}3 S752P. Once again, native {beta}3-/- pre-osteoclasts are protected against apoptosis. Similar to its effect on bone resorption, transduced wild type {beta}3 normalizes the apoptotic rate of {beta}3-/- pre-osteoclasts. Unexpectedly, however, {beta}3 S752P transductants also die at a rate indistinguishable from wild type. Thus, unoccupied {alpha}v{beta}3 integrin regulates osteoclast apoptosis via a component of the integrin different than that regulating resorption.
Key words: osteoclast • apoptosis • integrin • bone resorption • caspases




This article has been cited by other articles:


Home page
 EndocrinologyHome page
H. Liu, R. Yang, B. Tinner, A. Choudhry, N. Schutze, and B. Chaqour
Cysteine-Rich Protein 61 and Connective Tissue Growth Factor Induce Deadhesion and Anoikis of Retinal Pericytes
Endocrinology, April 1, 2008; 149(4): 1666 - 1677.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. L. Teitelbaum
Osteoclasts: What Do They Do and How Do They Do It?
Am. J. Pathol., February 1, 2007; 170(2): 427 - 435.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
F. J White, R. C Burghardt, J. Hu, M. M Joyce, T. E Spencer, and G. A Johnson
Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation.
Reproduction, December 1, 2006; 132(6): 919 - 929.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Maubant, D. Saint-Dizier, M. Boutillon, F. Perron-Sierra, P. J. Casara, J. A. Hickman, G. C. Tucker, and E. Van Obberghen-Schilling
Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells
Blood, November 1, 2006; 108(9): 3035 - 3044.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. W. Rinker-Schaeffer, J. P. O'Keefe, D. R. Welch, and D. Theodorescu
Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application.
Clin. Cancer Res., July 1, 2006; 12(13): 3882 - 3889.
[Full Text] [PDF]

Home page
 Mol. Interv.Home page
I. Podgorski and B. F. Sloane
Loss of Caspase-8 in Tumor Cells: Mechanism to Overcome Integrin-Mediated Death?
Mol. Interv., June 1, 2006; 6(3): 132 - 136.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2004 by The Endocrine Society