Mice Lacking the Type I Interleukin-1 Receptor Do Not Lose Bone Mass after Ovariectomy
Abstract
We measured the effects of ovariectomy on the bone mass of mice that lacked type I interleukin-1 receptor (IL-I R1 -/- mice) in two genetic backgrounds (C57BL/6 x 129/Sv and C57BL/6) to investigate the role of interleukin-1 in the actions of estrogen on bone. At three weeks after surgery, ovariectomized wild-type mice decreased trabecular bone volume in the proximal humerus by 70% in a C57BL/6 x 129/Sv background and 48% in a C57BL/6 background compared to sham-operated controls. In contrast, there was no significant decrease in trabecular bone mass in IL-1 R1 -/- mice after ovariectomy. The estrogen status of all groups was confirmed by measurement of uterine wet weight. These results demonstrate that a functional IL-1 response pathway is required for mice to lose trabecular bone mass after ovariectomy in this model and they imply that IL-1 is an important mediator of the effects of ovariectomy on bone mass. Hence, therapeutic interventions that block the effects of IL-1 on bone may be beneficial for treating diseases of rapid bone loss such as post-menopausal osteoporosis.
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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”
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- Authors
- Lorenzo, J. A., Naprta, A., Rao, Y., Alander, C., Glaccum, M., Widmer, M., Gronowicz, G., Kalinowski, J., & Pilbeam, C. C.
- Affiliations
- VA Connecticut Healthcare System (US)
- UConn Health (US)
- Immunex Research and Development Corporation (M.G., M.W.), Seattle, Washington 98101
- Corresponding author
- Lorenzo, Joseph A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-06-01
- Volume
- 139
- Issue
- 6
- Pages
- 3022-3025
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2019172276
- Cited by
- 185
- References
- 0
- Citations by year
- 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 7 · 2012: 8
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P01AR038933)
- 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
- ovariectomy, bone loss, trabecular bone mass, estrogen, postmenopausal osteoporosis, bone resorption, genetic background effects
- MeSH terms
- Animals, Female, Humerus, Organ Size, Ovariectomy, Postoperative Period, Reference Values, Uterus, Bone Density, Receptors, Interleukin-1, Mice, Knockout, Mice
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