FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.
FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.
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DOI：
10.1172/jci18399
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发表时间：
2003-09
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通讯作者：
M. Riminucci;M. Collins;N. Fedarko;Natasha Cherman;A. Corsi;K. White;S. Waguespack;Anurag Gupta;T. Hannon;M. Econs;P. Bianco;P. Gehron Robey
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作者：
M. Riminucci;M. Collins;N. Fedarko;Natasha Cherman;A. Corsi;K. White;S. Waguespack;Anurag Gupta;T. Hannon;M. Econs;P. Bianco;P. Gehron Robey
FGF-23是FGF家族的新成员，是常染色体显性遗传性低磷血症性佝偻病（ADHR）基因突变的产物。FGF-23被认为是一种循环因子，不仅在ADHR中（由于降解不足），而且在肿瘤诱导的骨软化症中（由于肿瘤细胞的过度合成）引起肾磷酸盐消耗。大约50%的McCune-Albright综合征（MAS）和骨纤维异常增殖症（FD）患者发生肾磷酸盐消耗，这是由GNAS 1基因的合子后突变引起的。我们发现，体内和体外正常和FD骨祖细胞和骨形成细胞均可产生FGF-23。FGF-23 mRNA表达的原位杂交分析确定了“纤维”细胞、成骨细胞和与微血管壁相关的细胞为FD中FGF-23的特异性细胞来源。与正常年龄匹配的对照组相比，FD/MAS患者的血清FGF-23水平升高，与无肾性磷酸盐消耗的FD/MAS患者相比，血清FGF-23水平显著升高，并与常用于评估疾病活动性的疾病负荷骨转换标志物相关。FD组织产生FGF-23可能在FD/MAS相关的肾性磷酸盐消耗综合征中起重要作用。
FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified "fibrous" cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.