ArticleBlood2023
Bone-derived C-terminal FGF23 cleaved peptides increase iron availability in acute inflammation.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 29 citations in OpenAlex.
- Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives.Bioactive materials · 2026Review
- Broken signals: when the mineralostat alters the cardiovascular system.Pediatric nephrology (Berlin, Germany) · 2026Review
- FGF23 - A hormone produced by bone and has many faces.Reviews in endocrine & metabolic disorders · 2026Review
- When X Does Not Mark the Spot: Autosomal Dominant and Recessive Forms of Renal Hypophosphatemic Rickets and Osteomalacia.Current osteoporosis reports · 2026Review
- Article
- Fibroblast growth factor 23 at the crossroads of mineral metabolism and bone disease.Current opinion in nephrology and hypertension · 2026Review
- 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
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Marked regression of calcinosis with canakinumab in hyperphosphatemic familial tumoral calcinosis.JBMR plus · 2026Article
- The renal response to FGF23 shifts from phosphaturia toward inflammation in kidney disease.Journal of cell communication and signaling · 2026Article
- The Interplay Between Bone Biology and Iron Metabolism: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- Anemia and iron deficiency in post-kidney transplantation: an unsolved challenge.Clinical kidney journal · 2025Review
- Fibroblast growth factor 23 as a risk factor for incident diabetes.Current opinion in nephrology and hypertension · 2025Review
- Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.Nature communications · 2025Article
- Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.Kidney international · 2025Article
- The Roxadustat (FG-4592) ameliorates tubulointerstitial fibrosis by promoting intact FGF23 cleavage.Cell communication and signaling : CCS · 2025Article
- Anemia in Elderly Patients: Contribution of Renal Aging and Chronic Kidney Disease.Geriatrics (Basel, Switzerland) · 2025Review
- C-terminal FGF-23 production coupling with aldosterone via FAM20C and predicting cardiovascular events in primary aldosteronism.JCI insight · 2025Article
- Iron and Bone Pathophysiology.Advances in experimental medicine and biology · 2025Review
- Iron deficiency and phlebotomy in patients with polycythemia vera.International journal of hematology · 2025Review
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14 authors at 3 institutions in 3 countries.
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Abstract
Inflammation leads to functional iron deficiency by increasing the expression of the hepatic iron regulatory peptide hepcidin. Inflammation also stimulates fibroblast growth factor 23 (FGF23) production by increasing both Fgf23 transcription and FGF23 cleavage, which paradoxically leads to excess in C-terminal FGF23 peptides (Cter-FGF23), rather than intact FGF23 (iFGF23) hormone. We determined that the major source of Cter-FGF23 is osteocytes and investigated whether Cter-FGF23 peptides play a direct role in the regulation of hepcidin and iron metabolism in response to acute inflammation. Mice harboring an osteocyte-specific deletion of Fgf23 showed a ∼90% reduction in Cter-FGF23 levels during acute inflammation. Reduction in Cter-FGF23 led to a further decrease in circulating iron in inflamed mice owing to excessive hepcidin production. We observed similar results in mice showing impaired FGF23 cleavage owing to osteocyte-specific deletion of Furin. We next showed that Cter-FGF23 peptides bind members of the bone morphogenetic protein (BMP) family, BMP2 and BMP9, which are established inducers of hepcidin. Coadministration of Cter-FGF23 and BMP2 or BMP9 prevented the increase in Hamp messenger RNA and circulating hepcidin levels induced by BMP2/9, resulting in normal serum iron levels. Finally, injection of Cter-FGF23 in inflamed Fgf23KO mice and genetic overexpression of Cter-Fgf23 in wild type mice also resulted in lower hepcidin and higher circulating iron levels. In conclusion, during inflammation, bone is the major source of Cter-FGF23 secretion, and independently of iFGF23, Cter-FGF23 reduces BMP-induced hepcidin secretion in the liver.
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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.