ArticleNature metabolism2019
Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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.
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Who cites it
44 citing papers in PubMed, 91 citations in OpenAlex.
- Increased fracture risk associated with iron-deficiency anemia: a population-based propensity score matched cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
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- Iron overload induced by ferric derisomaltose and ferric carboxymaltose both increase FGF-23 levels and lead to osteomalacia and bone loss in normal mice.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- The m6Am methyltransferase PCIF1 promotes osteogenic differentiation of mesenchymal stem cells through stabilization of Wnt-related transcripts.PLoS biology · 2026Article
- Cortical Bone Loss and Fragility in a 2-Month Triple Transgenic Mouse Model of Alzheimer's Disease.Cells · 2025Article
- Article
- Bone phenotype in male and female mice after knockdown of transferrin receptor 1 in osterix-expressing cells.JBMR plus · 2025Article
- Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling for Iron-Regulated Hematopoietic Stem and Progenitor Cells' Commitment toward Erythroid and Megakaryocytic Lineages.ACS pharmacology & translational science · 2025Article
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Liver function linked to bone health: A bibliometric of the liver-bone axis.World journal of hepatology · 2025Article
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Bone phenotyping of murine hemochromatosis models with deficiencies of Hjv, Alk2, or Alk3: The influence of sex and the bone compartment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- A glimpse into the future: Integrating artificial intelligence for precision HER2-positive breast cancer management.iMetaOmics · 2024Review
- Involvement of the Wnt/β-catenin signalling pathway in heterotopic ossification and ossification-related diseases.Journal of cellular and molecular medicine · 2024Review
- Interfaces between Cranial Bone and AISI 304 Steel after Long-Term Implantation: A Case Study of Cranial Screws.ACS biomaterials science & engineering · 2024Article
- The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.Neurochemical research · 2024Review
- Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts.Communications biology · 2024Article
- Biomimetic peroxidase MOF-Fe promotes bone defect repair by inhibiting TfR2 and activating the BMP2 pathway.Biology direct · 2024Article
- Comparison of the effects of high dietary iron levels on bone microarchitecture responses in the mouse strains 129/Sv and C57BL/6J.Scientific reports · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 12 institutions in 5 countries.
Funding
Abstract
Transferrin receptor 2 (Tfr2) is mainly expressed in the liver and controls iron homeostasis. Here, we identify Tfr2 as a regulator of bone homeostasis that inhibits bone formation. Mice lacking Tfr2 display increased bone mass and mineralization independent of iron homeostasis and hepatic Tfr2. Bone marrow transplantation experiments and studies of cell-specific Tfr2 knockout mice demonstrate that Tfr2 impairs BMP-p38MAPK signaling and decreases expression of the Wnt inhibitor sclerostin specifically in osteoblasts. Reactivation of MAPK or overexpression of sclerostin rescues skeletal abnormalities in Tfr2 knockout mice. We further show that the extracellular domain of Tfr2 binds BMPs and inhibits BMP-2-induced heterotopic ossification by acting as a decoy receptor. These data indicate that Tfr2 limits bone formation by modulating BMP signaling, possibly through direct interaction with BMP either as a receptor or as a co-receptor in a complex with other BMP receptors. Finally, the Tfr2 extracellular domain may be effective in the treatment of conditions associated with pathological bone formation.
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.