成纤维细胞生长因子23（Fibroblast growth factor 23, FGF-23）是重要的磷调节激素，目前其代谢相关调控机制并未完全阐明。FGF-23与多种代谢性骨病发生和慢性肾脏病（CKD）的预后密切相关。本课题根据常染色体隐性遗传性低血磷性佝偻病（ARHR2）和CKD患者软组织异位矿化和血FGF-23水平显著升高的共同临床特征，提出了“焦磷酸酶磷酸二酯酶1（NPP1）/焦磷酸盐（PPi）调控FGF-23代谢耦联平衡”的研究假设。将通过在体（ENPP1-/-、Dmp1-Cre-ENPP1-/-和CKD模型）和离体(成骨样UMR-106细胞系)研究NPP1/PPi对FGF-23代谢耦联的调控作用，并在CKD模型中观察缺铁对NPP1/PPi调控FGF-23代谢失衡的触发作用。本研究将为以FGF-23代谢失衡和异位钙化为特征的疾病(如动脉粥样硬化等)的防治提供新线索。

Fibroblast growth factor 23 (FGF-23) is a major phosphaturic hormone. The regulatory mechanism of FGF-23 metabolism remains uncovered. FGF-23 is closely related to the occurrence of several metabolic bone diseases and the prognosis of chronic kidney disease (CKD). The patients of autosomal recessive hypophosphatemic rickets 2 (ARHR2) and CKD share some common clinical features, which are ectopic calcification of soft tissue and obviously elevated serum FGF-23. Based on the previous studies, we hypothesized: 'the nucleotide pyrophosphatase phosphodiesterase 1(NPP1) and pyrophosphate (PPi) may play an important role on regulation of FGF-23 metabolic coupling'. ENPP1-/-, Dmp1-Cre-ENPP1-/- and CKD mice model, as well as osteoblasts liked cells will be involved in our study, to detect the changes of metabolic coupling for FGF-23 production and cleavage with NPP1/PPi intervention. The trigger effects of iron-deficiency on NPP1/PPi-FGF-23 regulatory axis in CKD model will also be investigated. This study will bring to light on the new intervention target for a group of disorders (e.g. CKD, atherosclerosis) which characterized by elevated FGF-23 level and ectopic calcification.