ArticleThe Journal of clinical investigation2021
Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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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.
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Who cites it
103 citing papers in PubMed, 133 citations in OpenAlex.
- Article
- Links between bone fractures and the gut microbiota.Nature reviews. Endocrinology · 2026Review
- Wubi Shanyao Pills ameliorate glucocorticoid-induced osteoporosis by regulating bone marrow T cell homing as an immune intermediate to restore bone metabolism.Chinese medicine · 2026Article
- Metabolically engineered probiotic OMVs as nanovaccine mediating sequential immunomodulation for chronic bone infection immunotherapy.Cell reports. Medicine · 2026Article
- Bacterial specificity of the gut microbiome predicts bone density in primary hyperparathyroidism.Bone research · 2026Article
- Article
- Dried Ginger Milk Extract Alleviates Inflammatory Bowel Disease-Associated Bone Loss via Gut Microbiota-Metabolite Remodeling and MEK/ERK Inhibition.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Gut microbiota and bone aging: Focusing on the gut-X axis modes.Journal of orthopaedic translation · 2026Review
- Cell Death in Orthodontic Tooth Movement: Recent Advances and Emerging Insights.International journal of molecular sciences · 2026Review
- Association between lymphocyte to high-density lipoprotein ratio and total bone mineral density in 8-19-year-old children and adolescents: a cross-sectional study.European journal of medical research · 2026Article
- Rewiring osteoimmune homeostasis in osteoporosis: T-cell subsets as key regulators and emerging therapeutic targets.Frontiers in immunology · 2026Review
- Raman spectroscopic fingerprinting uncovers a multi-scale structural-mechanical-transcriptomic coupling landscape in osteoporosis.Frontiers in endocrinology · 2026Article
- Uridine inhibits ROS-mediated osteoclast differentiation and alleviates osteoporosis via modulation of PI3K/Akt-FoxO signaling.Frontiers in immunology · 2026Article
- Gut microbiota-mediated Th17/Treg regulation in osteoporotic fracture: from postmenopausal dysbiosis to callus repair.Frontiers in immunology · 2026Review
- The role of gut microbiota-immune-endocrine crosstalk in the pathogenesis of osteoporosis.Frontiers in immunology · 2026Review
- Osteoporosis and gut microbiota: current understandings.Frontiers in immunology · 2026Review
- Osteoimmunology: interactions of the bone and immune system.Frontiers in immunology · 2026Review
- The potential role and research progress of the gut microbiota-NGF axis in postmenopausal bone homeostasis imbalance.Frontiers in immunology · 2026Review
- Estrogen signaling in PDGFRα+ cells positively regulates cortical bone metabolism via IGFBP5 in female mice.JBMR plus · 2026Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen deficiency causes a gut microbiome-dependent expansion of BM Th17 cells and TNF-α-producing T cells. The resulting increased BM levels of IL-17a (IL-17) and TNF stimulate RANKL expression and activity, causing bone loss. However, the origin of BM Th17 cells and TNF+ T cells is unknown. Here, we show that ovariectomy (ovx) expanded intestinal Th17 cells and TNF+ T cells, increased their S1P receptor 1-mediated (S1PR1-mediated) egress from the intestine, and enhanced their subsequent influx into the BM through CXCR3- and CCL20-mediated mechanisms. Demonstrating the functional relevance of T cell trafficking, blockade of Th17 cell and TNF+ T cell egress from the gut or their influx into the BM prevented ovx-induced bone loss. Therefore, intestinal T cells are a proximal target of sex steroid deficiency relevant for bone loss. Blockade of intestinal T cell migration may represent a therapeutic strategy for the treatment of postmenopausal bone loss.
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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.