Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism
Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism
复制标题
DOI：
10.1681/asn.2006070783
复制
发表时间：
2007-10-01
影响因子：
13.6
通讯作者：
Nishizawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Kawata, Takehisa;Imanishi, Yasuo;Nishizawa, Yoshiki
成纤维细胞生长因子23（FGF-23）在磷酸盐消耗性疾病发病机制中的重要性已经确定，但是关于也刺激尿磷酸盐排泄的甲状旁腺激素（PTH）如何调节FGF-23的循环水平仍然存在争议。我们发现，PTH-细胞周期蛋白D1转基因小鼠，原发性甲状旁腺功能亢进症的模型，血清FGF-23浓度高于野生型小鼠。在90- 118周龄小鼠中，血清FGF-23浓度与血清PTH和钙显著且直接相关，与磷酸盐水平呈负相关（均P < 0.005）。实时定量逆转录PCR显示fgf 23在骨中有丰富的表达，尤其是在颅骨中。与野生型小鼠相比，转基因小鼠中颅盖骨中的fgf 23表达显著更高，并且与血清FGF-23水平良好相关。FGF-23的表达与骨钙素和ALP的表达之间存在直接相关性，表明成骨细胞的活化在FGF-23的调节中是重要的。甲状旁腺切除术后转基因小鼠血清FGF-23水平降低。总之，PTH在原发性甲状旁腺功能亢进患者血清FGF-23水平的调节中起主要作用，可能是通过激活骨中的成骨细胞。
The importance of fibroblast growth factor 23 (FGF-23) in the pathogenesis of phosphate wasting disorders has been established, but controversy remains about how parathyroid hormone (PTH), which also stimulates urinary phosphate excretion, regulates the circulating level of FGF-23. We found that the serum FGF-23 concentration was higher in PTH-cyclin D1 transgenic mice, a model of primary hyperparathyroidism, than in wild-type mice. The serum FGF-23 concentration was significantly and directly correlated with serum PTH and calcium, and inversely correlated with phosphate levels in 90- to 118-week-old mice (all P < 0.005). Quantitative real-time reverse-transcriptase PCR revealed abundant expression of fgf23 in bone, especially in calvaria. The fgf23 expression in calvaria was significantly higher in the transgenic mice compared to the wild-type mice, and correlated well with serum FGF-23 levels. There was a direct correlation between the expression of fgf23 and the expression of osteocalcin and ALP, suggesting that activation of osteoblasts is important in the regulation of FGF-23. Serum FGF-23 levels decreased in the transgenic mice after parathyroidectomy. In conclusion, PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone.