Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period
Abstract
Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the production of cytokines in bone or bone marrow. However, controversy remains on the role of candidate factors, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). As IL-1 and TNF have many additive and/or synergistic effects in bone, we tested the hypothesis that the simultaneous block of IL-1 and TNF is required to prevent the initial phase of rapid bone loss that follows ovariectomy (ovx). To this aim, rats were ovariectomized and treated for 2 weeks with either IL-1 receptor antagonist (IL-1ra), an inhibitor of IL-1, or TNF-binding protein (TNFbp), an inhibitor of TNF. Ovx increased bone marrow cell secretion of IL-1 and TNF and decreased the bone density of the distal femur, as measured by dual energy x-ray absorptiometry. Ovx-induced bone loss was decreased by both IL-1ra and TNFbp and completely prevented by simultaneous treatment with IL-1ra and TNFbp. Combined treatment with IL-1ra and TNFbp decreased urinary pyridinoline cross-links, a marker of bone resorption that reflects osteoclast number and osteoclast activity, whereas treatment with either inhibitor alone was less effective. Both IL-1ra and TNFbp decreased the number of osteoclasts on the endocortical surfaces and stimulated bone formation, but the two inhibitors had no additive effects on these indexes, suggesting that inhibition of osteoclastogenesis and stimulation of bone formation do not account…
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In rodents, blocking IL-1 or TNF-α prevents ovariectomy bone loss, and mice lacking IL-1 receptor or TNF-α do not lose bone after ovariectomy.
“Bone loss after ovariectomy in rodent models can be prevented by inhibiting IL-1 or TNF-α and does not occur in mice deficient in the IL-1 receptor or TNF-α”
From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [26]
Cites
Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.
Pacifici, R., Rifas, L., McCracken, R., Vered, I., McMurtry, C., Avioli, L. V., & Peck, W. A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.7.2398 · Cited by 375 · see citing works
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Pathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779 · see citing works
Maier, S. F., & Watkins, L. R. (1998) · Psychological Review · doi:10.1037/0033-295x.105.1.83 · Cited by 1,130 · see citing works
Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts
Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., Harada, Y., Azuma, Y., Krust, A., Yamamoto, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.025 · Cited by 1,013 · see citing works
Requirement for NF-κB in osteoclast and B-cell development
Franzoso, G., Carlson, L., Xing, L., Poljak, L., Shores, E. W., Brown, K. D., Leonardi, A., Tran, T., Boyce, B. F., & Siebenlist, U. (1997) · Genes & Development · doi:10.1101/gad.11.24.3482 · Cited by 996 · see citing works
Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis
Pacifici, R. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110802 · Cited by 741 · see citing works
Self-citationRoggia, C., Gao, Y., Cenci, S., Weitzmann, M. N., Toraldo, G., Isaia, G., & Pacifici, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251534698 · Cited by 513 · see citing works
Self-citationInflammaging as a Major Characteristic of Old People: Can It Be Prevented or Cured?
Franceschi, C. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2007.tb00358.x · Cited by 342 · see citing works
Ammann, P., Rizzoli, R., Bonjour, J. P., Bourrin, S., Meyer, J. M., Vassalli, P., & Garcia, I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119333 · Cited by 310 · see citing works
The Functional Block of TNF but Not of IL-6 Prevents Bone Loss in Ovariectomized Mice
Kimble, R. B., Bain, S., & Pacifici, R. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.6.935 · Cited by 241 · see citing works
Self-citationMorony, S., Capparelli, C., Lee, R., Shimamoto, G., Boone, T., Lacey, D. L., & Dunstan, C. R. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.9.1478 · Cited by 187 · see citing works
Kostenuik, P. J., Capparelli, C., Morony, S., Adamu, S., Shimamoto, G., Shen, V., Lacey, D. L., & Dunstan, C. R. (2001) · Endocrinology · doi:10.1210/endo.142.10.8437 · Cited by 140 · see citing works
High TNF-α levels in resting B cells negatively correlate with their response
Frasca, D., Diaz, A., Romero, M., Landin, A. M., & Blomberg, B. B. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.004 · Cited by 115 · see citing works
Cline-Smith, A., Axelbaum, A., Shashkova, E., Chakraborty, M., Sanford, J., Panesar, P., Peterson, M., Cox, L., Baldan, A., Veis, D., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3966 · Cited by 108 · see citing works
Effects of calcitonin gene-related peptide on bone turnover in ovariectomized rats
Valentijn, K., Gutow, A. P., Troiano, N., Gundberg, C., Gilligan, J. P., & Vignery, A. (1997) · Bone · doi:10.1016/s8756-3282(97)00142-7 · Cited by 89 · see citing works
A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss
Goswami, J., Hernández‐Santos, N., Zuniga, L. A., & Gaffen, S. L. (2009) · European Journal of Immunology · doi:10.1002/eji.200939670 · Cited by 87 · see citing works
Gonzalez-Calvin, J. L., Gallego-Rojo, F., Fernandez-Perez, R., Casado-Caballero, F., Ruiz-Escolano, E., & Olivares, E. G. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0077 · Cited by 81 · see citing works
Kang, J. S., Yoon, Y. D., Han, M. H., Han, S.-B., Lee, K., Kang, M. R., Moon, E.-Y., Jeon, Y. J., Park, S.-K., & Kim, H. M. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.009 · Cited by 43 · see citing works
Shozu, M., Zhao, Y., & R. Simpson, E. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(99)00233-6 · Cited by 36 · see citing works
- Authors
- Kimble, R. B., Matayoshi, A. B., Vannice, J. L., Kung, V. T., Williams, C., & Pacifici, R.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1995-07
- Volume
- 136
- Issue
- 7
- Pages
- 3054-3061
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2165087809
- Cited by
- 273
- References
- 1
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 13 · 2014: 7 · 2013: 9 · 2012: 9
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041412, AR41412)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- interleukin-1, TNF-α, ovariectomy, estrogen deficiency, bone loss, interleukin-1 receptor antagonist, TNF-binding protein, bone resorption, osteoclasts, bone formation, pyridinoline, postmenopausal osteoporosis
- MeSH terms
- Animals, Bone Marrow, Bone Marrow Cells, Bone Resorption, Carrier Proteins, Cells, Cultured, Female, Humans, Interleukin-1, Ovariectomy, Sialoglycoproteins, Tumor Necrosis Factor-alpha, Absorptiometry, Photon, Bone Density, Osteoporosis, Postmenopausal, Rats, Sprague-Dawley, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Rats, Tumor Necrosis Factor Decoy Receptors, Interleukin 1 Receptor Antagonist Protein
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