This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Inoue, M. Articles by Teitelbaum, S. L. Search for Related Content PubMed PubMed Citation Articles by Inoue, M. Articles by Teitelbaum, S. L.

Tumor Necrosis Factor Regulates _vß₅ Integrin Expression by Osteoclast Precursors in Vitro and in Vivo¹

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Steven L. Teitelbaum, M.D., Department of Pathology, Washington University School of Medicine, Barnes-Jewish Hospital North, 216 South Kingshighway, St. Louis, Missouri 63110. E-mail: teitelbs{at}medicine.wustl.edu

Early osteoclast precursors, in the form of murine bone marrow macrophages (BMMs), while expressing no detectable _vß₃ integrin, contain abundant _vß₅ and attach to matrix in an _v integrin-dependent manner. Furthermore, _vß₅ expression by osteoclast precursors progressively falls as they assume the resorptive phenotype. We find the osteoclastogenic agent, tumor necrosis factor-, (TNF) down-regulates _vß₅ expression by BMMS via attenuation of ß₅ messenger RNA (mRNA) t1/2. Using BMMs from TNF receptor knockout mice we establish the p55 receptor transmits the ß₅ suppressive effect. The functional implications of TNF-mediated _vß₅ down-regulation are underscored by the capacity of an _v inhibitory peptide mimetic to prevent spreading by BMMs expressing abundant _vß₅ while failing to impact those in which the integrin has been diminished by TNF. Finally, ß₅ mRNA in BMMs of wild-type mice administered lipopolysaccharide (LPS) progressively falls with time of in vivo treatment. Alternatively, ß₅ mRNA does not decline in BMMs of LPS-treated mice lacking both TNF receptors, documenting down-regulation of the ß₅ integrin subunit, in vivo, is mediated by TNF. Thus, matrix attachment of osteoclast precursors and mature osteoclasts are governed by distinct _v integrins which are differentially regulated by specific cytokines.

This article has been cited by other articles:

				J. C. Crockett, N. Schutze, D. Tosh, S. Jatzke, A. Duthie, F. Jakob, and M. J. Rogers The Matricellular Protein CYR61 Inhibits Osteoclastogenesis by a Mechanism Independent of {alpha}v{beta}3 and {alpha}v{beta}5 Endocrinology, December 1, 2007; 148(12): 5761 - 5768. [Abstract] [Full Text] [PDF]

				Y.-L. Lin, W. J. S. de Villiers, B. Garvy, S. R. Post, T. R. Nagy, F. F. Safadi, M. C. Faugere, G. Wang, H. H. Malluche, and J. P. Williams The Effect of Class A Scavenger Receptor Deficiency in Bone J. Biol. Chem., February 16, 2007; 282(7): 4653 - 4660. [Abstract] [Full Text] [PDF]

				S. Shi, C. Nathan, D. Schnappinger, J. Drenkow, M. Fuortes, E. Block, A. Ding, T. R. Gingeras, G. Schoolnik, S. Akira, et al. MyD88 Primes Macrophages for Full-Scale Activation by Interferon-{gamma} yet Mediates Few Responses to Mycobacterium tuberculosis J. Exp. Med., October 6, 2003; 198(7): 987 - 997. [Abstract] [Full Text] [PDF]

				R L Wilder Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases Ann Rheum Dis, November 1, 2002; 61(90002): ii96 - 99. [Abstract] [Full Text] [PDF]