FGF23 directly inhibits osteoprogenitor differentiation in Dmp1-knockout mice

• DOI: 10.1172/jci.insight.156850
• Publication Date: 2023-11-09T17:00:17Z
• Authors: Guillaume Courbon; Dominik Kentrup; Jane Joy Thomas; Xueyan Wang; Hao-Hsuan Tsai; Jadeah Spindler; John Von Drasek; Laura Mazudie Ndj...; Marta Martinez-Calle; Sana Lynch; Lauriane Hivert; Xiaofang Wang; Wenhan Chang; Jian Q. Feng; Valentin David; Aline Martin
• Keywords: Hypophosphatemia; Osteomalacia; Hypophosphatemic Rickets; DMP1; PHEX; Osteocyte; Bone remodeling

Fibroblast growth factor 23 (FGF23) is a phosphate (Pi)-regulating hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal and osteomalacia. Blocking became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited autosomal recessive rickets (ARHR). This study investigates the effects of Pi repletion bone specific deletion Fgf23 on mineral metabolism Dmp1 knockout (Dmp1KO) mouse model ARHR.At 12 weeks, Dmp1KO mice showed increased serum PTH levels, growth, Six weeks dietary supplementation exacerbated production, hyperparathyroidism, renal excretion In contrast, osteocyte-specific resulted partial correction which was sufficient to fully restore only partially corrected phenotype. vitro, we show that directly impairs osteoprogenitors differentiation DMP1 deficiency contributes mineralization independently or levels.