Endocrinology, Vol 131, 2229-2234, Copyright © 1992 by Endocrine Society

ARTICLES

Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone

Y Ohsaki, S Takahashi, T Scarcez, A Demulder, T Nishihara, R Williams and GD Roodman
Veterans Administration Medical Center, San Antonio, Texas.

Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone-resorbing capacity of these cells.

This article has been cited by other articles:

				J. Lorenzo, M. Horowitz, and Y. Choi Osteoimmunology: Interactions of the Bone and Immune System Endocr. Rev., June 1, 2008; 29(4): 403 - 440. [Abstract] [Full Text] [PDF]

				G. Gamberi, M. S. Benassi, P. Ragazzini, L. Pazzaglia, F. Ponticelli, C. Ferrari, A. Balladelli, M. Mercuri, M. Gigli, F. Bertoni, et al. Proteases and interleukin-6 gene analysis in 92 giant cell tumors of bone Ann. Onc., March 1, 2004; 15(3): 498 - 503. [Abstract] [Full Text] [PDF]

				J.-H. Han, S. J. Choi, N. Kurihara, M. Koide, Y. Oba, and G. D. Roodman Macrophage inflammatory protein-1{alpha} is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor {kappa}B ligand Blood, June 1, 2001; 97(11): 3349 - 3353. [Abstract] [Full Text] [PDF]

				T. A. Hentunen, S. H. Jackson, H. Chung, S. V. Reddy, J. Lorenzo, S. J. Choi, and G. D. Roodman Characterization of Immortalized Osteoclast Precursors Developed from Mice Transgenic for Both bcl-XL and Simian Virus 40 Large T Antigen Endocrinology, July 1, 1999; 140(7): 2954 - 2961. [Abstract] [Full Text]

				O. A. Adebanjo, B. S. Moonga, T. Yamate, L. Sun, C. Minkin, E. Abe, and M. Zaidi Mode of Action of Interleukin-6 on Mature Osteoclasts. Novel Interactions with Extracellular Ca2+ Sensing in the Regulation of Osteoclastic Bone Resorption J. Cell Biol., September 7, 1998; 142(5): 1347 - 1356. [Abstract] [Full Text] [PDF]

				D. Inoue, P. Santiago, W. C. Horne, and R. Baron Identification of an Osteoclast Transcription Factor That Binds to the Human T Cell Leukemia Virus Type I-Long Terminal Repeat Enhancer Element J. Biol. Chem., October 3, 1997; 272(40): 25386 - 25393. [Abstract] [Full Text] [PDF]

				N. G. Arvidson, B. Gudbjörnsson, A. Larsson, and R. Hällgren The timing of glucocorticoid administration in rheumatoid arthritis Ann Rheum Dis, January 1, 1997; 56(1): 27 - 31. [Abstract] [Full Text]

				E. Jimi, T. Ikebe, N. Takahashi, M. Hirata, T. Suda, and T. Koga Interleukin-1alpha Activates an NF-kappaB-like Factor in Osteoclast-like Cells J. Biol. Chem., March 1, 1996; 271(9): 4605 - 4608. [Abstract] [Full Text] [PDF]

				S. C. Manolagas and R. L. Jilka Bone Marrow, Cytokines, and Bone Remodeling -- Emerging Insights into the Pathophysiology of Osteoporosis N. Engl. J. Med., February 2, 1995; 332(5): 305 - 311. [Full Text] [PDF]