ArticleProceedings of the National Academy of Sciences of the United States of America2001
Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
191 citing papers in PubMed, 1 synthesis or guideline pooled it, 509 citations in OpenAlex.
- Mechanisms and traditional Chinese medicine therapeutics for primary osteoporosis: an integrated perspective.Frontiers in endocrinology · 2025Pooled it
- Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss.Annals of the rheumatic diseases · 2009Trial
- Regulation of bone turnover by sex steroids in men.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2008Trial
- TLR4-dependent upregulation of IL-22-producing T cells in the bone niche links to the imbalance of bone homeostasis.Cellular & molecular biology letters · 2026Article
- The risk of osteoporosis in COPD: An analysis of sex differences and mediating effects based on NHANES.NPJ primary care respiratory medicine · 2026Article
- The influence of hormonal changes during pregnancy on bone metabolism - a mini review.Frontiers in endocrinology · 2026Review
- Osteoimmune senescence in aging bone: from inflammaging dogma to cell-type-specific therapeutic windows.Frontiers in immunology · 2026Review
- The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.Current osteoporosis reports · 2025Review
- High-fat diet, intestinal microecology and bone loss.Nutrition & metabolism · 2025Review
- CD8a + GZMK + T Cells Inhibit Osteoclastogenesis in Postmenopausal Osteoporosis via the p38-MAPK Pathway.Calcified tissue international · 2025Article
- Molecular mechanisms and treatment strategies for estrogen deficiency-related and glucocorticoid-induced osteoporosis: a comprehensive review.Inflammopharmacology · 2025Review
- Sex-dependent variation in bone adaptation: from degeneration to regeneration.Journal of orthopaedic translation · 2025Review
- Combined Sequential Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss and Estrogen Deficiency Bone Loss Are Cumulative in Mice Models.The Journal of infectious diseases · 2025Article
- Osteoimmunology: Crosstalk Between T Cells and Osteoclasts in Osteoporosis.Clinical reviews in allergy & immunology · 2025Review
- Article
- Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells.BMC musculoskeletal disorders · 2024Article
- 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
- Bone-organ axes: bidirectional crosstalk.Military Medical Research · 2024Review
- Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure.Particle and fibre toxicology · 2024Article
- A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).Frontiers in medicine · 2024Article
131 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
In vivo studies have shown T cells to be central to the mechanism by which estrogen deficiency induces bone loss, but the mechanism involved remains, in part, undefined. In vitro, T cells from ovariectomized mice produce increased amounts of tumor necrosis factor (TNF), which augments receptor activator of NF-kappa B ligand (RANKL)-induced osteoclastogenesis. However, both the mechanism and the relevance of this phenomenon in vivo remain to be established. In this study, we found that ovariectomy increased the number of bone marrow T cell-producing TNF without altering production of TNF per T cell. Attesting to the essential contribution of TNF, ovariectomy induced rapid bone loss in wild type (wt) mice but failed to do so in TNF-deficient (TNF(-/-)) mice. Furthermore, ovariectomy induced bone loss, which was absent in T cell-deficient nude mice, was restored by adoptive transfer of wt T cells, but not by reconstitution with T cells from TNF(-/-) mice. These findings demonstrate the key causal role of T cell-produced TNF in the bone loss after estrogen withdrawal. Finally, ovariectomy caused bone loss in wt mice and in mice lacking p75 TNF receptor but failed to do so in mice lacking the p55 TNF receptor. These findings demonstrate that enhanced T cell production of TNF resulting from increased bone marrow T cell number is a key mechanism by which estrogen deficiency induces bone loss in vivo. The data also demonstrate that the bone-wasting effect of TNF in vivo is mediated by the p55 TNF receptor.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.