Endocrinology, Vol 125, 1142-1150, Copyright © 1989 by Endocrine Society

ARTICLES

Effects of interleukin-1 on bone turnover in normal mice

BF Boyce, TB Aufdemorte, IR Garrett, AJ Yates and GR Mundy
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.

Interleukin-1 (IL-1) is a potent stimulator of osteoclastic bone resorption in vitro and causes hypercalcemia and increased osteoclastic resorption when infused into normal mice for 72 h. However, its longer term or local effects on bone turnover in vivo are unknown. To study these, we injected IL-1 alpha once daily for 3 days into the sc tissue over the calvariae of normal mice and examined its effects on calvarial bone morphology during the subsequent 4 weeks using quantitative histomorphometry. Increased bone resorption inside the calvariae and elevated plasma calcium concentrations were present 24 h after the last IL-1 injection. These early systemic effects were not prevented by indomethacin. During the following 3-4 weeks most of the bone on the injected side of the calvariae was resorbed by osteoclasts and was subsequently replaced by increased amounts of new bone. These longer term local effects on bone turnover were prevented by indomethacin. However, indomethacin did not prevent the formation of new bone inside the calvariae at sites of resorption induced by IL-1 independent of prostaglandin production. These findings indicate that IL-1 stimulates bone turnover systemically, independent of prostaglandin production, and that it has profound long term local effects on bone turnover that are mediated through prostaglandins.

This article has been cited by other articles:

				Z. Yao, L. Xing, C. Qin, E. M. Schwarz, and B. F. Boyce Osteoclast Precursor Interaction with Bone Matrix Induces Osteoclast Formation Directly by an Interleukin-1-mediated Autocrine Mechanism J. Biol. Chem., April 11, 2008; 283(15): 9917 - 9924. [Abstract] [Full Text] [PDF]

				Y. Niki, H. Takaishi, J. Takito, T. Miyamoto, N. Kosaki, H. Matsumoto, Y. Toyama, and N. Tada Administration of Cyclooxygenase-2 Inhibitor Reduces Joint Inflammation but Exacerbates Osteopenia in IL-1{alpha} Transgenic Mice Due to GM-CSF Overproduction J. Immunol., July 1, 2007; 179(1): 639 - 646. [Abstract] [Full Text] [PDF]

				H. Kaneki, R. Guo, D. Chen, Z. Yao, E. M. Schwarz, Y. E. Zhang, B. F. Boyce, and L. Xing Tumor Necrosis Factor Promotes Runx2 Degradation through Up-regulation of Smurf1 and Smurf2 in Osteoblasts J. Biol. Chem., February 17, 2006; 281(7): 4326 - 4333. [Abstract] [Full Text] [PDF]

				G A Clines and T A Guise Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone Endocr. Relat. Cancer, September 1, 2005; 12(3): 549 - 583. [Abstract] [Full Text] [PDF]

				B. O. Oyajobi, G. Franchin, P. J. Williams, D. Pulkrabek, A. Gupta, S. Munoz, B. Grubbs, M. Zhao, D. Chen, B. Sherry, et al. Dual effects of macrophage inflammatory protein-1{alpha} on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease Blood, July 1, 2003; 102(1): 311 - 319. [Abstract] [Full Text] [PDF]

				N E Lane and Q Rehman Osteoporosis in the rheumatic disease patient Lupus, October 1, 2002; 11(10): 675 - 679. [Abstract] [PDF]

				M. Ulrich-Vinther, E. E. Carmody, J. J. Goater, K. Søballe, R. J. O'Keefe, and E. M. Schwarz Recombinant Adeno-Associated Virus-Mediated Osteoprotegerin Gene Therapy Inhibits Wear Debris-Induced Osteolysis J. Bone Joint Surg. Am., August 12, 2002; 84(8): 1405 - 1412. [Abstract] [Full Text] [PDF]

				L. Li, A. Khansari, L. Shapira, D. T. Graves, and S. Amar Contribution of Interleukin-11 and Prostaglandin(s) in Lipopolysaccharide-Induced Bone Resorption In Vivo Infect. Immun., July 1, 2002; 70(7): 3915 - 3922. [Abstract] [Full Text] [PDF]

				I. Nakamura, Y. Kadono, H. Takayanagi, E. Jimi, T. Miyazaki, H. Oda, K. Nakamura, S. Tanaka, G. A. Rodan, and L. T. Duong IL-1 Regulates Cytoskeletal Organization in Osteoclasts Via TNF Receptor-Associated Factor 6/c-Src Complex J. Immunol., May 15, 2002; 168(10): 5103 - 5109. [Abstract] [Full Text] [PDF]

				J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]

				D.T. Graves, M. Oskoui, S. Voleinikova, G. Naguib, S. Cai, T. Desta, A. Kakouras, and Y. Jiang Tumor Necrosis Factor Modulates Fibroblast Apoptosis, PMN Recruitment, and Osteoclast Formation in Response to P. gingivalis Infection Journal of Dental Research, October 1, 2001; 80(10): 1875 - 1879. [Abstract] [PDF]

				S. Kamolmatyakul, W. Chen, and Y.-P. Li Interferon-{gamma} Down-regulates Gene Expression of Cathepsin K in Osteoclasts and Inhibits Osteoclast Formation Journal of Dental Research, January 1, 2001; 80(1): 351 - 355. [Abstract] [PDF]

				J. E. Compston Sex Steroids and Bone Physiol Rev, January 1, 2001; 81(1): 419 - 447. [Abstract] [Full Text] [PDF]

				A. E. Hak, H. A. P. Pols, A. M. van Hemert, A. Hofman, and J. C. M. Witteman Progression of Aortic Calcification Is Associated With Metacarpal Bone Loss During Menopause : A Population-Based Longitudinal Study Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1926 - 1931. [Abstract] [Full Text] [PDF]

				X. Li, Y. Okada, C. C. Pilbeam, J. A. Lorenzo, C. R. J. Kennedy, R. M. Breyer, and L. G. Raisz Knockout of the Murine Prostaglandin EP2 Receptor Impairs Osteoclastogenesis in Vitro Endocrinology, June 1, 2000; 141(6): 2054 - 2061. [Abstract] [Full Text] [PDF]

				J. Li, I. Sarosi, X.-Q. Yan, S. Morony, C. Capparelli, H.-L. Tan, S. McCabe, R. Elliott, S. Scully, G. Van, et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism PNAS, February 15, 2000; 97(4): 1566 - 1571. [Abstract] [Full Text] [PDF]

				T. Miyazaki, H. Katagiri, Y. Kanegae, H. Takayanagi, Y. Sawada, A. Yamamoto, M. P. Pando, T. Asano, I. M. Verma, H. Oda, et al. Reciprocal Role of ERK and NF-{kappa}B Pathways in Survival and Activation of Osteoclasts J. Cell Biol., January 24, 2000; 148(2): 333 - 342. [Abstract] [Full Text] [PDF]

				G. Mundy, R. Garrett, S. Harris, J. Chan, D. Chen, G. Rossini, B. Boyce, M. Zhao, and G. Gutierrez Stimulation of Bone Formation in Vitro and in Rodents by Statins Science, December 3, 1999; 286(5446): 1946 - 1949. [Abstract] [Full Text]

				N. Tani-Ishii, A. Tsunoda, T. Teranaka, and T. Umemoto Autocrine Regulation of Osteoclast Formation and Bone Resorption by IL-1{alpha} and TNF{alpha} Journal of Dental Research, October 1, 1999; 78(10): 1617 - 1623. [Abstract] [PDF]

				S. J. Choi, S. V. Reddy, R. D. Devlin, C. Menaa, H. Chung, B. F. Boyce, and G. D. Roodman Identification of Human Asparaginyl Endopeptidase (Legumain) as an Inhibitor of Osteoclast Formation and Bone Resorption J. Biol. Chem., September 24, 1999; 274(39): 27747 - 27753. [Abstract] [Full Text] [PDF]

				C.-Y. Chiang, G. Kyritsis, D. T. Graves, and S. Amar Interleukin-1 and Tumor Necrosis Factor Activities Partially Account for Calvarial Bone Resorption Induced by Local Injection of Lipopolysaccharide Infect. Immun., August 1, 1999; 67(8): 4231 - 4236. [Abstract] [Full Text] [PDF]

				T.W. Oates, J.-E. Xie, S. Clinton, A.M. Hoang, D.T. Graves, and D.L. Cochran PDGF-{alpha} Receptor Subunit Expression Down-regulated by IL-1{beta} in Human Periodontal Ligament Cells Journal of Dental Research, October 1, 1998; 77(10): 1791 - 1798. [Abstract] [PDF]

				Y. Zubery, C. R. Dunstan, B. M. Story, L. Kesavalu, J. L. Ebersole, S. C. Holt, and B. F. Boyce Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin Infect. Immun., September 1, 1998; 66(9): 4158 - 4162. [Abstract] [Full Text] [PDF]

				E. Jimi, I. Nakamura, T. Ikebe, S. Akiyama, N. Takahashi, and T. Suda Activation of NF-kappa B Is Involved in the Survival of Osteoclasts Promoted by Interleukin-1 J. Biol. Chem., April 10, 1998; 273(15): 8799 - 8805. [Abstract] [Full Text] [PDF]

				T. A. Guise and G. R. Mundy Cancer and Bone Endocr. Rev., February 1, 1998; 19(1): 18 - 54. [Abstract] [Full Text]

				P. L. Schwartzberg, L. Xing, O. Hoffmann, C. A. Lowell, L. Garrett, B. F. Boyce, and H. E. Varmus Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice Genes & Dev., November 1, 1997; 11(21): 2835 - 2844. [Abstract] [Full Text] [PDF]

				N. Shimizu, T. Goseki, M. Yamaguchi, T. Iwasawa, H. Takiguchi, and Y. Abiko In vitro Cellular Aging Stimulates Interleukin-1{beta} Production in Stretched Human Periodontal-ligament-derived Cells Journal of Dental Research, July 1, 1997; 76(7): 1367 - 1375. [Abstract] [PDF]

				E. Izbicka, T. Yoneda, Y. Takaoka, D. Horn, P. Williams, and G. R. Mundy Identification of a Novel Bone/Calcium Metabolism-regulating Factor in Porcine Pancreas J. Biol. Chem., September 20, 1996; 271(38): 23230 - 23234. [Abstract] [Full Text] [PDF]

				G.E. Wise and F. Lin Concise Review: The Molecular Biology of Initiation of Tooth Eruption Journal of Dental Research, January 1, 1995; 74(1): 303 - 306. [PDF]

				R. J. van't Hof, K. J. Armour, L. M. Smith, K. E. Armour, X. Q. Wei, F. Y. Liew, and S. H. Ralston Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption PNAS, July 5, 2000; 97(14): 7993 - 7998. [Abstract] [Full Text] [PDF]