ArticleProceedings of the National Academy of Sciences of the United States of America2004
Estrogen prevents bone loss through transforming growth factor beta signaling in T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 177 citations in OpenAlex.
- Inflammatory responses improve with milk ribonuclease-enriched lactoferrin supplementation in postmenopausal women.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2010Trial
- Letrozole in the extended adjuvant setting: MA.17.Breast cancer research and treatment · 2007Trial
- Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.International journal of molecular sciences · 2026Review
- Research Trends in Immunomodulatory Therapy for Postmenopausal Osteoporosis: A Bibliometric Analysis.Orthopaedic surgery · 2025Review
- Exploring the association between bioelectrical impedance parameters and body composition in women with and without dysmenorrhea and postmenopause.Physiological reports · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Recent advances in research on common targets of neurological and sex hormonal influences on asthma.Clinical and translational allergy · 2025Review
- Advances on T cell immunity in bone remodeling and bone regeneration.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Differential Gene Expression Involved in Bone Turnover of Mice Expressing Constitutively Active TGFβ Receptor Type I.International journal of molecular sciences · 2024Article
- Sex hormones and allergies: exploring the gender differences in immune responses.Frontiers in allergy · 2024Review
- Low-Dose Staphylococcal Enterotoxin C2 Mutant Maintains Bone Homeostasis via Regulating Crosstalk between Bone Formation and Host T-Cell Effector Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Role of Sex Differences in Bone Health and Healing.Biology · 2023Review
- Sohlh1 loss of function male and female infertility model impacts overall health beyond gonadal dysfunction in mice†.Biology of reproduction · 2023Article
- Effects of Estrogens on Osteoimmunology: A Role in Bone Metastasis.Frontiers in immunology · 2022Review
- Effect of Lymphocyte Subsets on Bone Density in Senile Osteoporosis: A Retrospective Study.Journal of immunology research · 2022Article
- New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.Molecules (Basel, Switzerland) · 2021Review
- Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss.iScience · 2021Article
- From the gut to bone: connecting the gut microbiota with Th17 T lymphocytes and postmenopausal osteoporosis.The Journal of clinical investigation · 2021Article
- Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells.The Journal of clinical investigation · 2021Article
- Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.Genome biology · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Estrogen (E) deficiency leads to an expansion of the pool of tumor necrosis factor (TNF)-producing T cells through an IFN-gamma-dependent pathway that results in increased levels of the osteoclastogenic cytokine TNF in the bone marrow. Disregulated IFN-gamma production is instrumental for the bone loss induced by ovariectomy (ovx), but the responsible mechanism is unknown. We now show that mice with T cell-specific blockade of type beta transforming growth factor (TGFbeta) signaling are completely insensitive to the bone-sparing effect of E. This phenotype results from a failure of E to repress IFN-gamma production, which, in turn, leads to increased T cell activation and T cell TNF production. Furthermore, ovx blunts TGFbeta levels in the bone marrow, and overexpression of TGFbeta in vivo prevents ovx-induced bone loss. These findings demonstrate that E prevents bone loss through a TGFbeta-dependent mechanism, and that TGFbeta signaling in T cells preserves bone homeostasis by blunting T cell activation. Thus, stimulation of TGFbeta production in the bone marrow is a critical "upstream" mechanism by which E prevents bone loss, and enhancement of TGFbeta levels in vivo may constitute a previously undescribed therapeutic approach for preventing bone loss.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.