Work

Fibroblast growth factor 23 neutralizing antibody partially rescues bone loss and increases hematocrit in sickle cell disease mice

Year: 2025

Type: article

Abstract: Fibroblast Growth Factor 23 (FGF23) is increased in serum of humanized Sickle Cell Disease (SCD) mice. Since FGF23 is associated with impaired bone formation, we examined the effect of FGF23-neutralizing antibody (FGF23Ab) on bone loss in SCD mice. Healthy control (Ctrl) and SCD 5-months-old female mice were treated with FGF23Ab or isotype-specific IgG for 6 weeks. Significantly reduced hematocrit in SCD mice was increased by FGF23Ab. MicroCT of SCD femurs revealed no significant reduction in metaphyseal bone volume/total volume vs. Ctrl mice. However, histomorphometry of SCD femur revealed significantly reduced mineral apposition rate, bone formation rate, inter-label thickness, and osteoid surface, which were increased by FGF23Ab. Significantly increased osteoclast number/bone perimeter in SCD mice was reduced by FGF23Ab. Bone marrow stromal cells (BMSC) cultured in osteogenic media revealed significantly reduced mineralized nodules in SCD-IgG-BMSC that was increased in SCD-FGF23Ab-BMSC. FGF23 and αKlotho protein was significantly increased in SCD-IgG-BMSC and was not reduced by FGF23Ab. However, phosphorylated FGF Receptor-1, the receptor through which FGF23 signals, was significantly reduced by FGF23Ab. The mineralization inhibitor osteopontin was significantly increased in SCD-IgG-BMSC cultures and was reduced by FGF23Ab. We conclude that FGF23Ab may be efficacious in improving some parameters of reduced bone formation in female SCD mice.

Source: Scientific Reports

DOI: 10.1038/s41598-025-95335-w

Authors: Liping Xiao, Wei He, Marja M. Hurley

Institution: UConn Health

Language: English

Topic: Parathyroid Disorders and Treatments

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690