FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH.
FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH.
复制标题
DOI：
10.1002/jbmr.433
复制
发表时间：
2011-09
影响因子：
6.2
通讯作者：
Lanske, Beate
中科院分区：
文献类型：
--
作者：
Yuan, Quan;Sato, Tadatoshi;Densmore, Michael;Saito, Hiroaki;Schueler, Christiane;Erben, Reinhold G.;Lanske, Beate
PTH被广泛认为是矿物质离子稳态的关键调节剂。每日间歇性给予PTH是目前唯一可用的骨疾病如骨质疏松症的合成代谢疗法。最近的研究表明，PTH增加成纤维细胞生长因子23（FGF 23）的转录和分泌，FGF 23是磷酸盐稳态和骨骼代谢的另一个重要调节因子。然而，PTH和FGF 23之间的全部关系在很大程度上是未知的。本研究评估了FGF 23/Klotho信号传导对PTH磷酸尿和合成代谢功能的影响。8日龄野生型（WT）、Fgf 23 −/−和Kl−/−小鼠每天注射100 µg/kg PTH（1-34）或溶剂，持续2周，然后处死。间歇注射PTH成功降低了Fgf 23 −/−和Kl−/−小鼠的血清磷酸盐水平，并逆转了高磷酸盐血症。通过pQCT、µCT和组织形态计量学分析股骨远端干骺端的骨变化。PTH治疗诱导每种小鼠基因型的骨矿物质密度（BMD）和骨小梁体积显著增加。成骨细胞标记基因的表达，包括Runx 2，Col 1，Alp，Ocn和Sost也发生了类似的变化。此外，分离原代成骨细胞，并在体外用100 nM PTH处理。PTH处理同样诱导cAMP积累和磷酸化的ERK 1/2和CREB的成骨细胞从每个基因型。综上所述，我们的结果表明，Fgf 23/Klotho信号传导对于PTH的磷酸尿和合成代谢功能不是必需的，这表明即使在存在异常血清FGF 23水平的情况下，PTH也可以作为治疗剂来改善患者的骨骼质量。
PTH is widely recognized as a key regulator of mineral ion homeostasis. Daily intermittent administration of PTH is the only currently available anabolic therapy for bone disorders such as osteoporosis. Recent studies have shown that PTH increases transcription and secretion of fibroblast growth factor 23 (FGF23), another important regulator of phosphate homeostasis and skeletal metabolism. However, the full relationship between PTH and FGF23 is largely unknown. This study evaluated the effect of FGF23/Klotho signaling on the phosphaturic and anabolic functions of PTH. Eight-day-old wild-type (WT), Fgf23−/− and Kl−/− mice were injected with 100 µg/kg PTH (1–34) or vehicle daily for a two-week-period and then sacrificed. Intermittent injection of PTH successfully reduced the serum phosphate levels and reversed the hyperphosphatemia of Fgf23−/− and Kl−/− mice. Bone changes were analyzed in the distal femur metaphysis by pQCT, µCT, and histomorphometry. PTH treatment induced substantial increases in bone mineral density (BMD) and trabecular bone volume in each mouse genotype. Expression of osteoblastic marker genes, including Runx2, Col1, Alp, Ocn and Sost were similarly altered. In addition, primary osteoblasts were isolated and treated with 100nM PTH in vitro. PTH treatment similarly induced cAMP accumulation and phosphorylation of ERK1/2 and CREB in the osteoblasts from each genotype. Taken together, our results demonstrate that Fgf23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH, suggesting that PTH can function as a therapeutic agent to improve the skeletal quality of patients even in the presence of abnormal serum FGF23 levels.
登录
查看更多内容
影响因子：
6.2
作者：
Burnett-Bowie, Sherri-Ann M.;Henao, Maria P.;Leder, Benjamin Z.
通讯作者：
Leder, Benjamin Z.
影响因子：
4.8
作者：
Chan, GK;Deckelbaum, RA;Karaplis, AC
通讯作者：
Karaplis, AC
影响因子：
4.8
作者：
Guo, Jun;Liu, Minlin;Kronenberg, Henry M.
通讯作者：
Kronenberg, Henry M.
DOI：
10.1152/ajpendo.00502.2004
发表时间：
2005-06-01
影响因子：
5.1
作者：
Ito, M;Sakai, Y;Miyamoto, K
通讯作者：
Miyamoto, K
影响因子：
15.9
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
通讯作者：
Manolagas, SC