Parathyroid hormone (1-34) (human)|52232-67-4|安捷凯

Background

Parathyroid hormone (1-34) (human) is the N-terminal fragment (34 amino acids) of human Parathyroid hormone (PTH) and is an agonist of the Parathyroid hormone 1 (PTH1) receptor^[1]. PTH is essential for the regulation of extracellular Ca²⁺ and phosphate metabolism^[2]. Parathyroid hormone (1-34) (human) can be used to treat osteoporosis. Injection of Parathyroid hormone (1-34) (human) can increase bone formation and bone mass without causing hypercalcemia^{[3, 4]}.

In vitro, Parathyroid hormone (1-34) (human) (0, 1, 10, 100nM) treatment of primary human osteoblasts for 24h induced an increase in angiopoietin 1 (Ang-1) mRNA expression. The 10nM dose increased the expression of Ang-1 mRNA by 2-fold (207%±6.4), but increasing the dose to 100nM did not further increase the expression level of Ang-1 mRNA^[5].

In vivo, subcutaneous administration of Parathyroid hormone (1-34) (human) (20μg/kg/day) to mature rabbits for 4 weeks increased the cortical bone porosity, number and density, as well as the cortical area, thickness and bone mineral content (BMC) of the distal femoral shaft, but had no significant effect on volumetric bone mineral density (BMD)^[6].

参考文献:
[1]?Hoare S R J, Usdin T B. Molecular mechanisms of ligand recognition by parathyroid hormone 1 (PTH1) and PTH2 receptors[J]. Current pharmaceutical design, 2001, 7(8): 689-713.
[2]?Goltzman D. Physiology of parathyroid hormone[J]. Endocrinology and Metabolism Clinics, 2018, 47(4): 743-758.
[3]?Kim E S, Keating G M. Recombinant human parathyroid hormone (1–84): a review in hypoparathyroidism[J]. Drugs, 2015, 75: 1293-1303.
[4]?Neer R M, Arnaud C D, Zanchetta J R, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis[J]. New England journal of medicine, 2001, 344(19): 1434-1441.
[5]?Park J H, Song H I, Rho J M, et al. Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast-like cells[J]. Experimental and clinical endocrinology & diabetes, 2006, 114(08): 438-443.
[6] Iwamoto J, Seki A, Nango N. Influence of teriparatide and ibandronate on cortical bone in New Zealand white rabbits: A HR-QCT study[J]. Calcified tissue international, 2016, 99(5): 535-542.

Parathyroid hormone (1-34) (human)是人类甲状旁腺激素（PTH）的N端片段（34个氨基酸），是甲状旁腺激素1（PTH1）受体的激动剂^[¹^]。PTH对于细胞外Ca²⁺和磷酸盐代谢的调节至关重要^[²^]。Parathyroid hormone (1-34) (human)可用于治疗骨质疏松症，注射Parathyroid hormone (1-34) (human)可以增加骨形成和骨量，而不会引起高钙血症^[^{3, 4}^]。

在体外，Parathyroid hormone (1-34) (human)（0, 1, 10, 100nM）处理原代人类成骨细胞24h，诱导了血管生成素1（Ang-1）mRNA表达增加。10nM剂量下使Ang-1 mRNA的表达增加了2倍（207%±6.4），但剂量提高至100nM不会进一步增加Ang-1 mRNA表达水平^[⁵^]。

在体内，Parathyroid hormone (1-34) (human)（20μg/kg/day）通过皮下注射治疗成熟家兔4周，增加了股骨远端骨干的皮质骨孔隙比、数量和密度以及皮质面积、厚度和骨矿物质含量（BMC），但对体积骨矿物质密度（BMD）没有显著影响^[⁶^]。

Protocol

Cell experiment [1]:

Cell lines

Primary cultured human osteoblasts

Preparation Method

Primary cultured human osteoblasts were cultured in the presence of 0, 1, 10, and 100nM Parathyroid hormone (1-34) (human) for 24h. The expression of Ang-1 mRNA was analyzed by RT-PCR.

Reaction Conditions

0, 1, 10, 100nM; 24h

Applications

Parathyroid hormone (1-34) (human) induced an increase in Ang-1 mRNA expression. The Ang-1 mRNA levels, at 10nM Parathyroid hormone (1-34) (human), were 2-fold (207%±6.4) the levels of the control. Further increases in the concentration of Parathyroid hormone (1-34) (human) (to 100nM) did not further increase the levels of Ang-1 mRNA expression.

Animal experiment [2]:

Animal models

Female New Zealand white rabbits

Preparation Method

Rabbits were randomized into six groups of 7 animals each as follows: 4-week vehicle administration group, 4-week Parathyroid hormone (1-34) (human) (TPTD) administration group (20μg/kg/day, s.c.), 12-week vehicle administration group, 4-week TPTD administration+8-week vehicle administration group, 4-week TPTD administration+8-week lower-dose ibandronate (IBN) administration group (20μg/kg, s.c., every 4 weeks), and 4-week TPTD administration+8-week higher-dose IBN administration group (100μg/kg, s.c., every 4 weeks). After the 4- or 12-week experimental period, the cortical bone of the distal femoral diaphysis was processed for HR-QCT analysis.?

Dosage form

20μg/kg/day, for 4 weeks; s.c.

Applications

Parathyroid hormone (1-34) (human) administration increased the pore ratio, number, and density as well as the cortical area, thickness, and bone mineral content (BMC), without significant influencing the volumetric bone mineral density (BMD).

参考文献:
[1]Park J H, Song H I, Rho J M, et al. Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast-like cells[J]. Experimental and clinical endocrinology & diabetes, 2006, 114(08): 438-443.
[2]Iwamoto J, Seki A, Nango N. Influence of teriparatide and ibandronate on cortical bone in New Zealand white rabbits: A HR-QCT study[J]. Calcified tissue international, 2016, 99(5): 535-542.

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Parathyroid hormone (1-34) (human)

Parathyroid hormone (1-34) (human)详情

Background

Protocol

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