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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2044-2050. Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2004-03-1196. This Article Full Text (PDF) All Versions of this Article: 2004-03-1196v1 104/7/2044    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zauli, G. Articles by Secchiero, P. Search for Related Content PubMed PubMed Citation Articles by Zauli, G. Articles by Secchiero, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2004 Accepted May 28, 2004 TNF-related apoptosis inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL+M-CSF Giorgio Zauli, Erika Rimondi, Vanessa Nicolin, Elisabetta Melloni, Claudio Celeghini, and Paola Secchiero* Department of Normal Human Morphology, University of Trieste, Trieste, Italy Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy * Corresponding author; email: secchier{at}mail.umbi.umd.edu. The role of the TNF-superfamily member receptor activator of nuclear factor kappa B ligand (RANKL) in promoting the differentiation of osteoclasts has been extensively characterized. In this study, we have investigated the effect of TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF-superfamily of cytokines, in osteoclastogenesis, by using human peripheral blood mononuclear cells and the RAW264.7 murine monocytic cell line. Both cell models differentiate into osteoclast-like cells in presence of RANKL+macrophage-colony stimulating factor (M-CSF), as evaluated in terms of TRAP-positive multinucleated cells and bone resorption activity. Unexpectedly, when added in culture in combination with RANKL+M-CSF, TRAIL inhibited osteoclastic differentiation in both cell models. To investigate the molecular mechanism underlining such inhibitory activity, we have analyzed the effect of TRAIL on the mitogen-activated protein kinases (MAPKs) pathways, which play a key role in osteoclastogenesis. Treatment with RANKL+M-CSF activated both the ERK1/2 and p38/MAPK pathways, which are essential for proliferation and differentiation of preosteoclasts, respectively. Of note, the addition of TRAIL to RANKL+M-CSF did not affect ERK1/2 but it profoundly inhibited p38/MAPK phosphorylation. Thus, our data demonstrate that TRAIL blocks osteoclastic differentiation and suggest that inhibition of the p38/MAPK pathway by TRAIL likely plays an important role in this process. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Stuck on the TRAIL of osteoclast differentiation Elizabeth Olmsted Davis Blood 2004 104: 1914-1915. [Full Text] [PDF] This article has been cited by other articles: P. Secchiero, E. Melloni, M. G. di Iasio, M. Tiribelli, E. Rimondi, F. Corallini, V. Gattei, and G. Zauli Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism Blood, April 30, 2009; 113(18): 4300 - 4308. [Abstract] [Full Text] [PDF] A. Labrinidis, P. Diamond, S. Martin, S. Hay, V. Liapis, I. Zinonos, N. A. Sims, G. J. Atkins, C. Vincent, V. Ponomarev, et al. Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma Clin. Cancer Res., March 15, 2009; 15(6): 1998 - 2009. [Abstract] [Full Text] [PDF] F. Corallini, F. Bossi, A. Gonelli, C. Tripodo, G. Castellino, T. E. Mollnes, F. Tedesco, L. Rizzi, F. Trotta, G. Zauli, et al. The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: implications in rheumatoid arthritis Rheumatology, March 1, 2009; 48(3): 293 - 298. [Abstract] [Full Text] [PDF] G Castellino, F Corallini, F Trotta, and P Secchiero Is there any role for tumour necrosis factor related apoptosis inducing ligand-osteoprotegerin (TRAIL-OPG) interaction in rheumatoid arthritis? Ann Rheum Dis, August 1, 2008; 67(8): 1196 - 1197. [Full Text] [PDF] A. Labrinidis, V. Liapis, L. M. Thai, G. J. Atkins, C. Vincent, S. Hay, N. A. Sims, A. C. W. Zannettino, D. M. Findlay, and A. Evdokiou Does Apo2L/TRAIL play any physiologic role in osteoclastogenesis? Blood, June 1, 2008; 111(11): 5411 - 5412. [Full Text] [PDF] G. Zauli and P. Secchiero Role of TRAIL in osteoclastogenesis Blood, June 1, 2008; 111(11): 5413 - 5413. [Full Text] [PDF] C. Lorz, A. Benito-Martin, A. Boucherot, A. C. Ucero, M. P. Rastaldi, A. Henger, S. Armelloni, B. Santamaria, C. C. Berthier, M. Kretzler, et al. The Death Ligand TRAIL in Diabetic Nephropathy J. Am. Soc. Nephrol., May 1, 2008; 19(5): 904 - 914. [Abstract] [Full Text] [PDF] S. Vitovski, J. S. Phillips, J. Sayers, and P. I. Croucher Investigating the Interaction between Osteoprotegerin and Receptor Activator of NF-{kappa}B or Tumor Necrosis Factor-related Apoptosis-inducing Ligand: EVIDENCE FOR A PIVOTAL ROLE FOR OSTEOPROTEGERIN IN REGULATING TWO DISTINCT PATHWAYS J. Biol. Chem., October 26, 2007; 282(43): 31601 - 31609. [Abstract] [Full Text] [PDF] K. K. Frick, K. LaPlante, and D. A. Bushinsky RANK ligand and TNF-{alpha} mediate acid-induced bone calcium efflux in vitro Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1005 - F1011. [Abstract] [Full Text] [PDF] P. Valverde, T. Kawai, and M.A. Taubman Potassium Channel-blockers as Therapeutic Agents to Interfere with Bone Resorption of Periodontal Disease Journal of Dental Research, June 1, 2005; 84(6): 488 - 499. [Abstract] [Full Text] [PDF]

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