PTHrP 1-141 and 1-86 increase in vitro bone formation.
PTHrP 1-141 and 1-86 increase in vitro bone formation.
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DOI：
10.1016/j.jss.2010.02.023
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Toribio RE
中科院分区：
文献类型：
--
作者：
Hildreth BE 3rd;Werbeck JL;Thudi NK;Deng X;Rosol TJ;Toribio RE
甲状旁腺素相关蛋白（PTHrP）在骨中具有合成代谢作用，这导致了PTHrP和PTH的N-末端片段的临床使用。由于10-20%的骨折表现出愈合并发症，骨质疏松症仍然是一种使人衰弱的疾病，因此骨形成剂的开发至关重要。由于有证据表明PTHrP的N-末端以外的区域可能具有骨形成作用，因此本研究旨在比较全长PTHrP 1-141与N-末端PTHrP 1-86对体外骨形成的作用。每6天用5、25和50 pM PTHrP 1-141或1-86处理MC 3 T3-E1前成骨细胞一次，持续36天，持续1或24小时。还在单独和组合地阻断PTHrP的N-末端、核定位序列（NLS）和C-末端后处理细胞。测量矿化面积、碱性磷酸酶（ALP）和骨钙素（OCN）。PTHrP 1-141和1-86在24小时处理后增加矿化，但不增加1小时。用PTHrP 1-141处理24小时，而不是1-86，导致ALP浓度依赖性增加，1小时后无影响。暴露于两种肽1或24小时诱导OCN浓度依赖性增加，24小时超过1小时。抗体阻断显示NLS和C-末端是合成代谢的。PTHrP 1-141和1-86均增加体外骨形成;然而，PTHrP 1-141更有效。NLS和C-末端具有不同于N-末端的合成代谢作用。这证明了PTHrP 1-141作为骨骼合成代谢剂的优势。
Parathyroid hormone-related protein (PTHrP) has anabolic effects in bone, which has led to the clinical use of N-terminal fragments of PTHrP and PTH. Since 10-20% of fractures demonstrate healing complications and osteoporosis continues to be a debilitating disease, the development of bone-forming agents is of utmost importance. Due to evidence that regions of PTHrP other than the N-terminus may have bone-forming effects, this study was designed to compare the effects of full-length PTHrP 1-141 to N-terminal PTHrP 1-86 on in vitro bone formation. MC3T3-E1 pre-osteoblasts were treated once every 6 days for 36 days with 5, 25, and 50 pM of PTHrP 1-141 or 1-86 for 1 or 24 hours. Cells were also treated after blocking the N-terminus, the nuclear localization sequence (NLS), and the C-terminus of PTHrP, individually and in combination. Area of mineralization, alkaline phosphatase (ALP), and osteocalcin (OCN) were measured. PTHrP 1-141 and 1-86 increased mineralization after 24-hr treatments, but not 1-hr. PTHrP 1-141 was more potent than 1-86. Treatment with PTHrP 1-141 for 24-hr, but not 1-86, resulted in a concentration-dependent increase in ALP, with no effect after 1-hr. Exposure to both peptides for 1- or 24-hrs induced a concentration-dependent increase in OCN, with 24-hr exceeding 1-hr. Antibody blocking revealed that the NLS and C-terminus are anabolic. Both PTHrP 1-141 and 1-86 increased in vitro bone formation; however, PTHrP 1-141 was more effective. The NLS and C-terminus have anabolic effects distinct from the N-terminus. This demonstrates the advantage of PTHrP 1-141 as a skeletal anabolic agent.
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影响因子：
4.2
作者：
de Gortazar, A. R.;Alonso, V.;Esbrit, P.
通讯作者：
Esbrit, P.
影响因子：
4.8
作者：
Dobnig, H;Turner, RT
通讯作者：
Turner, RT
影响因子：
6.2
作者：
Schiller, PC;D'Ippolito, G;Howard, GA
通讯作者：
Howard, GA
影响因子：
3
作者：
Jüppner, H
通讯作者：
Jüppner, H
DOI：
10.1073/pnas.93.26.15233
发表时间：
1996-12-24
影响因子：
11.1
作者：
Kovacs, CS;Lanske, B;Kronenberg, HM
通讯作者：
Kronenberg, HM