Mineralized tissue cells are a principal source of FGF23
Mineralized tissue cells are a principal source of FGF23
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DOI：
10.1016/j.bone.2007.01.017
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发表时间：
2007-06-01
期刊：
影响因子：
4.1
通讯作者：
Maeda, Norihiko
中科院分区：
文献类型：
--
作者：
Yoshiko, Yuji;Wang, Hua;Maeda, Norihiko
虽然成纤维细胞生长因子（FGF）23被认为是遗传性和/或获得性低磷酸盐血症疾病中的磷酸尿因子，但它也在正常磷酸盐稳态中起内分泌作用。FGF 23对NaPi 2a协同转运蛋白和25-羟基D-3-1 α-羟化酶起负作用，导致肾磷酸盐（Pi）重吸收减少，而成骨细胞似乎是FGF 23的主要来源，其表达被1 α，25-二羟基维生素D-3（1，25（OH）（2）D-3）反向上调。在这里，我们已经显示了正常大鼠骨和牙齿中FGF 23的分布，以及其在胎鼠颅骨（RC）细胞培养物中的表达谱。FGF 23 mRNA在多个胎儿和成人组织中可检测到，但与其他测试组织相比，在成人颅骨、股骨和切牙中的水平高得多。免疫反应性FGF 23主要定位于成骨细胞、成牙骨质细胞和成牙本质细胞，在一些软骨细胞、骨细胞和牙骨质细胞中零星标记。值得注意的是，还发现破骨细胞是FGF 23的可能来源。胎儿骨和牙胚细胞的标记强度远低于年轻成人成骨细胞和成牙本质细胞。在RC细胞模型中，FGF 23在成骨细胞发育过程中表达。在β-甘油磷酸（β GP）诱导的基质矿化过程中，FGF 23表达短暂上调，然后下降至低于非β GP处理的对应物的水平。1，25（OH）（2）D-3显著增加FGF 23的表达，同时抑制GP诱导的矿化。我们的数据表明，骨中的FGF 23表达与体外和体内的骨形成密切相关，并指出FGF 23在年轻成人而不是胎儿矿化组织中作为Pi稳态的系统因子的重要作用。(c)2007年爱思唯尔公司All rights reserved.
While fibroblast growth factor (FGF) 23 is known as a phosphaturic factor in inherited and/or acquired hypophosphatemic disorders, it also serves an endocrine role in nonrial phosphate homeostasis. FGF23 acts negatively on the NaPi2a cotransporter and 25-hydroxy D-3-1 alpha-hydroxylase with a resultant decrease in renal phosphate (Pi) reabsorption, while osteoblasts appear to be a primary source of FGF23 whose expression is counter-upregulated by 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3). Here we have shown the distribution of FGF23 in normal rat bone and tooth, and its expression profile in fetal rat calvaria (RC) cell cultures. FGF23 mRNA was detectable in multiple fetal and adult tissues but levels were much higher in adult calvaria, femur and incisor, compared to the other tissues tested. Immunoreactive FGF23 was predominantly localized to osteoblasts, cementoblasts, and odontoblasts, with sporadic labeling in some chondrocytes, osteocytes and cementocytes. Notably, osteoclasts were also found to be a possible source of FGF23. Fetal bone and tooth germ cells labeled much less intensely than young adult osteoblasts and odontoblasts. In the RC cell model, FGF23 was expressed during osteoblast development. During matrix mineralization induced by beta-glycerophosphate (beta GP), FGF23 expression was transiently upregulated and then decreased to levels lower than in their non-beta GP-treated counterparts. 1,25(OH)(2)D-3 markedly increased FGF23 expression concomitant with the inhibition of GP-induced mineralization. Our data suggest that FGF23 expression in bone is closely correlated with bone formation in vitro and vivo, and points towards an important role(s) for FGF23 in young adult but not fetal mineralized tissues as a systemic factor for Pi homeostasis. (c) 2007 Elsevier Inc. All rights reserved.