The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β
Abstract
Postmenopausal osteoporosis, the most common bone disease in the developed world, is associated with estrogen deficiency. This deficiency induces increased generation and activity of osteoclasts, which perforate bone trabeculae, thus reducing their strength and increasing fracture risk. Estrogen replacement prevents these effects, indicating that estrogen negatively regulates osteoclast formation and function, but how it does this is unclear. Because functional osteoclast life span and thus the amount of bone that osteoclasts resorb could also be enhanced following estrogen deficiency, and since sex steroids regulate apoptosis in other target tissues, we investigated whether estrogen may affect osteoclast function by promoting apoptosis. 17 beta-Estradiol promoted apoptosis of murine osteoclasts in vitro and in vivo by two- to threefold. Tamoxifen, which has estrogenic effects on bone resorption, and transforming growth factor-beta 1 (TGF-beta), whose production by osteoblasts is increased by estrogen, had similar effects in vitro. Anti-TGF-beta antibody inhibited TGF-beta-, estrogen- and tamoxifen-induced osteoclast apoptosis, indicating that TGF-beta might mediate this effect. These findings suggest that estrogen may prevent excessive bone loss before and after the menopause by limiting osteoclast life span through promotion of apoptosis. The development of analogues to promote this mechanism specifically could be a useful and novel therapeutic approach to prevent postmenopausal osteoporosis.
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In the citing paper
“The estrogen suppresses the osteoclast formation and activity as well as induces osteoclast apoptosis [16, 76, 104, 154].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [154]
In the citing paper
“The estrogen suppresses the osteoclast formation and activity as well as induces osteoclast apoptosis [16, 76, 104, 154].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [154]
In the citing paper
“In addition, estrogen can also increase TGF-β and osteoprotegerin (OPG) levels, which inhibit osteoclast differentiation [[58], [59], [60]].”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [60]
Citations
Cites
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Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6
Jilka, R. L., Hangoc, G., Girasole, G., Passeri, G., Williams, D. C., Abrams, J. S., Boyce, B. F., Broxmeyer, H. E., & Manolagas, S. C. (1992) · Science · doi:10.1126/science.1621100 · Cited by 1,440
Self-citationBisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D., Mundy, G. R., & Boyce, B. F. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101008 · Cited by 1,039
Self-citationBone acid phosphatase: Tartrate-resistant acid phosphatase as a marker of osteoclast function
Minkin, C. (1982) · Calcified Tissue International · doi:10.1007/bf02411252 · Cited by 992
Continuous c-fos expression precedes programmed cell death in vivo
Smeyne, R. J., Vendrell, M., Hayward, M. D., Baker, S. J., Miao, G. G., Schilling, K., Robertson, L. M., Curran, T., & Morgan, J. I. (1993) · Nature · doi:10.1038/363166a0 · Cited by 775
Takahashi, N., Yamana, H., Yoshiki, S., Roodman, G. D., Mundy, G. R., Jones, S. J., BOYDE, A., & Suda, T. (1988) · Endocrinology · doi:10.1210/endo-122-4-1373 · Cited by 731
Self-citationPerspectives: How many women have osteoporosis now?
Melton, J. L. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100202 · Cited by 596
Cytokines and Estrogen in Bone: Anti-Osteoporotic Effects
Horowitz, M. C. (1993) · Science · doi:10.1126/science.8480174 · Cited by 451
Tashjian, A. H., Voelkel, E. F., Lazzaro, M., Singer, F. R., Roberts, A. B., Derynck, R., Winkler, M. E., & Levine, L. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4535 · Cited by 381
Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.
Erlebacher, A., & Derynck, R. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.132.1.195 · Cited by 372
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Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,639
“an effect seemingly mediated by TGFb (139).”
BackgroundOsteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
“Some systemic and local factors that regulate development and interplay between osteoclasts and osteoblasts have been identified (Mundy 1993a,b; Erlebacher and Derynck 1996; Manolagas and Jilka 1995; Hughes et al. 1996; Pacifici 1996).”
BackgroundBiology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
“These cells exhibit a thin and flat nuclear profile; its cytoplasm extends along the bone surface and displays few cytoplasmic organelles such as profiles of rough endoplasmic reticulum and Golgi apparatus [50] (Figure 2(b)).”
BackgroundPathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779
Metadata
- Authors
- Hughes, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., & Boyce, B. F.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- ORCID
- Boyce, Brendan F.
- Venue
- Nature Medicine
- Published
- 1996-10
- Volume
- 2
- Issue
- 10
- Pages
- 1132-1136
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2016674232
- Cited by
- 813
- References
- 27
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 13 · 2023: 20 · 2022: 23 · 2021: 24 · 2020: 23 · 2019: 22 · 2018: 22 · 2017: 15 · 2016: 22 · 2015: 27 · 2014: 16 · 2013: 29 · 2012: 27
- FWCI
- 14.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ar039529-07)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 45299)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 43510, AR 39529, R01AR043510)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- estrogen, osteoclast apoptosis, TGF-beta, postmenopausal osteoporosis, estradiol, tamoxifen, bone resorption, estrogen deficiency, anti-TGF-beta antibody, estrogen replacement therapy, bone loss prevention
- MeSH terms
- Animals, Bone and Bones, Bone Resorption, Cell Count, Cells, Cultured, Estradiol, Estrogen Antagonists, Female, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Organ Size, Osteoblasts, Osteoclasts, Ovariectomy, Tamoxifen, Uterus, Osteoporosis, Postmenopausal, Transforming Growth Factor beta, Apoptosis, Mice
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