Kawata Takehisa, Imanishi Yasuo, Kobayashi Keisuke, Miki Takami, Arnold Andrew, Inaba Masaaki, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
J Am Soc Nephrol. 2007 Oct;18(10):2683-8. doi: 10.1681/ASN.2006070783. Epub 2007 Sep 12.
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.
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得到证实，但对于同样刺激尿磷排泄的甲状旁腺激素（PTH）如何调节FGF - 23的循环水平仍存在争议。我们发现，在原发性甲状旁腺功能亢进模型PTH - 细胞周期蛋白D1转基因小鼠中，血清FGF - 23浓度高于野生型小鼠。在90至118周龄的小鼠中，血清FGF - 23浓度与血清PTH和钙显著正相关，与磷水平负相关（所有P < 0.005）。定量实时逆转录PCR显示fgf23在骨骼中大量表达，尤其是在颅骨中。与野生型小鼠相比，转基因小鼠颅骨中的fgf23表达显著更高，且与血清FGF - 23水平密切相关。fgf23的表达与骨钙素和碱性磷酸酶的表达直接相关，表明成骨细胞的激活在FGF - 23的调节中很重要。甲状旁腺切除术后，转基因小鼠的血清FGF - 23水平降低。总之，在原发性甲状旁腺功能亢进中，PTH可能通过激活骨中的成骨细胞，在血清FGF - 23水平的调节中起主要作用。
