Osteopenia Related FGF23 Upregulation In Patients With Congenital Scoliosis

Objective: Congenital scoliosis(CS),a complex spinal malformation of unknown etiology with abnormal bone formation and metabolism,has a global prevalence of 0.5–1‰.Fibroblast growth factor 23(FGF23),a hormone secreted by osteoblasts and osteocytes,is important for bone metabolism.The relationship between CS and FGF23 remains unclear.In this study,DNA methylation sequencing was used to search for genes causing bone mineral density reduction in patients with CS,which were verified in the population of patients with CS,and the possible related mechanisms were explored.Methods: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region;one twin in each pair had CS,and the other developed normally.We then measured FGF23 m RNA levels in 20 CS patients’ and 23 age-matched controls’ peripheral blood by quantitative PCR and correlated FGF23 m RNA levels with clinical characteristics.Receiver operator curves(ROCs)were used to analyze the sensitivity and specificity of FGF23 m RNA levels for different characteristics.q PCR and western blotting of the inferior facet joint bone from CS patients and controls were performed to verify FGF23 protein expression and OPG/RANKL,an important marker of osteogenic ability.Results: DNA methylation of the FGF23 gene in CS patient peripheral blood was decreased compared to that of their identical twin,and m RNA levels were increased.Blood FGF23 m RNA levels were significantly increased in CS patients compared to controls subsequent analysis.ROC curves showed that FGF23 m RNA levels accurately predicted CS.q PCR and WB showed significantly increased FGF23 levels in CS patient primary osteoblasts,and OPG/RANKL was lower than in the control group,indicating inhibited osteogenic ability.Conclusion: FGF23 levels in the blood and inferior facet joint bone were significantly higher in CS patients due to low FGF23 DNA methylation.FGF23 m RNA levels in peripheral blood could be a biomarker for CS.In addition,upregulation of FGF23 potentially impaired osteogenesis by inhibiting OPG/RANKL,and led to low bone mineral density.