| First Author | Aprile A | Year | 2023 |
| Journal | Sci Transl Med | Volume | 15 |
| Issue | 698 | Pages | eabq3679 |
| PubMed ID | 37256933 | Mgi Jnum | J:336374 |
| Mgi Id | MGI:7488325 | Doi | 10.1126/scitranslmed.abq3679 |
| Citation | Aprile A, et al. (2023) Inhibition of FGF23 is a therapeutic strategy to target hematopoietic stem cell niche defects in beta-thalassemia. Sci Transl Med 15(698):eabq3679 |
| abstractText | Clinical evidence highlights a relationship between the blood and the bone, but the underlying mechanism linking these two tissues is not fully elucidated. Here, we used beta-thalassemia as a model of congenital anemia with bone and bone marrow (BM) niche defects. We demonstrate that fibroblast growth factor 23 (FGF23) is increased in patients and mice with beta-thalassemia because erythropoietin induces FGF23 overproduction in bone and BM erythroid cells via ERK1/2 and STAT5 pathways. We show that in vivo inhibition of FGF23 signaling by carboxyl-terminal FGF23 peptide is a safe and efficacious therapeutic strategy to rescue bone mineralization and deposition in mice with beta-thalassemia, normalizing the expression of niche factors and restoring hematopoietic stem cell (HSC) function. FGF23 may thus represent a molecular link connecting anemia, bone, and the HSC niche. This study provides a translational approach to targeting bone defects and rescuing HSC niche interactions, with potential clinical relevance for improving HSC transplantation and gene therapy for hematopoietic disorders. |
