低磷血症
内分泌学
内科学
成纤维细胞生长因子23
浪费的
苯丙氨酸
成纤维细胞生长因子
医学
生物
甲状旁腺激素
佝偻病
受体
维生素D与神经学
钙
作者
Rocío Fuente,Eva‐Maria Pastor‐Arroyo,Nicole Gehring,Patricia Oro Carbajosa,Laura Alonso‐Durán,Ivan Zderic,James Tapia-Dean,Ahmad Kamal Hamid,Carla Bettoni,Fernando Santos,Carsten A. Wagner,Isabel Rubio‐Aliaga
摘要
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone. X-linked hypophosphatemia (XLH) is the most prevalent inherited phosphate wasting disorder due to mutations in the PHEX gene, which cause elevated circulating FGF23 levels. Clinically, it is characterized by growth impairment and defective mineralization of bones and teeth. Treatment of XLH is challenging. Since 2018, neutralizing antibodies against FGF23 have dramatically improved the therapy of XLH patients, although not all patients fully respond to the treatment, and it is very costly. C-terminal fragments of FGF23 have recently emerged as blockers of intact FGF23 signaling. Here, we analyzed the effect on growth and bone of a short 26 residues long C-terminal FGF23 (cFGF23) fragment and two N-acetylated and C-amidated cFGF23 peptides using young XLH mice (Phex C733RMhda mice). Although no major changes in blood parameters were observed after 7 days of treatment with these peptides, bone length and growth plate structure improved. The modified peptides accelerated the growth rate probably by improving growth plate structure and dynamics. The processes of chondrocyte proliferation, death, hypertrophy, and the cartilaginous composition in the growth plate were partially improved in young treated XLH mice. In conclusion, these findings contribute to understand the role of FGF23 signaling in growth plate metabolism and show that this may occur despite continuous hypophosphatemia.
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