pTH-Related Protein (1-34) (human, mouse, rat) is a peptide with a conserved sequence among human, mouse, and rat species. pTH-Related Protein (1-34) shares significant homology with parathyroid hormone (PTH) and binds to the same PTH receptor, participating in various physiological processes[1]. In the regulation of calcium and phosphate metabolism, pTH-Related Protein (1-34) acts on the kidneys and bones. In the kidneys, pTH-Related Protein (1-34) promotes calcium reabsorption and reduces phosphate reabsorption, helping to maintain appropriate levels of calcium and phosphate in the blood[2]. In bone tissue, pTH-Related Protein (1-34) initially stimulates osteoblast activity, promoting bone formation. However, persistent and excessive activation of pTH-Related Protein (1-34) may also lead to bone resorption by indirectly activating osteoclasts[3]. pTH-Related Protein (1-34) also affects cell proliferation. In some cancer cells, abnormal expression of pTH-Related Protein (1-34) may contribute to tumor growth and metastasis[4].
In vitro, pTH-Related Protein (1-34) (10nM) was used to treat UMR106-01 cells (an osteoblastic cell line) by brief exposure (12 minutes) followed by washout, inducing sustained cAMP generation and persistent activation of the cAMP/PKA signaling pathway, as well as sustained upregulation of several CREB-responsive genes (c-Fos, IL-6, RANKL, Bglap1)[5]. pTH-Related Protein (1-34) (human, mouse, rat) was also used at a concentration of 10nM to treat the human breast cancer cell line MCF7. pTH-Related Protein (1-34) increased cell proliferation levels but did not alter p27 protein expression levels[6].
In vivo, pTH-Related Protein (1-34) (human, mouse, rat) (0.2µg/day) was administered via subcutaneous injection to 25-hydroxyvitamin D-1α-hydroxylase and PTH double knockout mice (starting from postnatal day 4 for 10 days or up to 1 month). pTH-Related Protein (1-34) significantly increased serum calcium levels in the mice, alleviated severe hypocalcemia, and prolonged survival. pTH-Related Protein (1-34) enhanced renal calcium reabsorption by increasing renal calcium transport protein expression, leading to increased long bone length, enlarged epiphyseal volume, enhanced proliferation and differentiation of growth plate chondrocytes, and increased cartilage matrix mineralization[7]. Four-month-old male C57Bl/6J mice were given subcutaneous injections of pTH-Related Protein (1-34) (human, mouse, rat) (80µg/kg/day) for 6 weeks, resulting in increased mineral density in the tooth roots of the mice[8].
References:
[1] Suva LJ, Winslow GA, Wettenhall RE, et al. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science. 1987 Aug 21;237(4817):893-6.
[2] Chen T, Wang Y, Hao Z, et al. Parathyroid hormone and its related peptides in bone metabolism. Biochem Pharmacol. 2021 Oct;192:114669.
[3] Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002 Aug;2(8):584-93.
[4] Johnson RW, Rhoades J, Martin TJ. Parathyroid hormone-related protein in breast cancer bone metastasis. Vitam Horm. 2022;120:215-230.
[5] Ho PWM, Chan AS, Pavlos NJ, et al. Brief exposure to full length parathyroid hormone-related protein (PTHrP) causes persistent generation of cyclic AMP through an endocytosis-dependent mechanism. Biochem Pharmacol. 2019 Nov;169:113627.
[6] Edwards CM, Kane JF, Smith JA, et al. PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR. Breast Cancer Res. 2024 Feb 26;26(1):34.
[7] Xue Y, Zhang Z, Karaplis AC, et al. Exogenous PTH-related protein and PTH improve mineral and skeletal status in 25-hydroxyvitamin D-1alpha-hydroxylase and PTH double knockout mice. J Bone Miner Res. 2005 Oct;20(10):1766-77.
[8] Hsu C, He Z, Le Henaff C, et al. Differential effects of parathyroid hormone, parathyroid hormone-related protein, and abaloparatide on collagen 1 expression by mouse cementoblasts and mouse tooth root density. Am J Orthod Dentofacial Orthop. 2023 Mar;163(3):378-388.
pTH-Related Protein (1-34) (human, mouse, rat)是一种在人、小鼠和大鼠物种间具有保守序列的肽。pTH-Related Protein (1-34)与甲状旁腺激素（PTH）具有显著的同源性，并与相同的PTH受体结合，参与多种生理过程[1]。在钙磷代谢调节方面，pTH-Related Protein (1-34)作用于肾脏和骨骼。在肾脏中，pTH-Related Protein (1-34)促进钙的重吸收并减少磷的重吸收，有助于维持血液中适当的钙磷水平[2]。在骨组织中，早期pTH-Related Protein (1-34)刺激成骨细胞活性，促进骨形成。然而，持续和过度的pTH-Related Protein (1-34)激活也可能通过间接激活破骨细胞导致骨吸收 [3]。pTH-Related Protein (1-34)还对细胞增殖有影响。在一些癌细胞中，pTH-Related Protein (1-34)异常表达可能有助于肿瘤的生长和转移[4]。
在体外，pTH-Related Protein (1-34) (human, mouse, rat)（10nM）通过短暂暴露（12分钟）后洗脱的方式处理UMR106-01细胞（一种成骨细胞系），诱导了cAMP的持续生成，还导致了cAMP/PKA信号通路的持续激活，持续激活以及多个CREB响应基因（c-Fos、IL-6、RANKL、Bglap1）的持续上调 [5]。pTH-Related Protein (1-34) (human, mouse, rat)以10 nM的浓度处理人乳腺癌细胞系MCF7。pTH-Related Protein (1-34)增加了细胞的增殖水平但不引起p27蛋白表达水平变化[6]。
在体内，pTH-Related Protein (1-34) (human, mouse, rat)（0.2µg/天）通过皮下注射给予25-羟维生素D-1α-羟化酶和pTH双敲除小鼠（从出生后第4天开始，持续10天或至1个月）。pTH-Related Protein (1-34)显著提高了小鼠的血清钙水平，改善了严重的低钙血症，并延长了小鼠的生存时间，pTH-Related Protein (1-34)通过增加肾钙转运蛋白的表达，促进了肾钙重吸收，长骨长度增加、骨骺体积增大、生长板软骨细胞增殖和分化增强，以及软骨基质矿化增加[7]。4个月大的雄性C57Bl/6J小鼠接受皮下注射pTH-Related Protein (1-34) (human, mouse, rat)（80μg/kg/天），持续6周，pTH-Related Protein (1-34)增加了小鼠牙齿根部的矿化密度[8]。