Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.
Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.
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重组人甲状旁腺激素相关蛋白1-34和1-84及其在骨质疏松症治疗中的作用
DOI：
10.1371/journal.pone.0088237
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Wang H;Liu J;Yin Y;Wu J;Wang Z;Miao D;Sun W
骨质疏松症是一种常见的疾病，其特征是骨骼强度受损，使患者容易发生骨折。甲状旁腺激素相关蛋白(PTHrP)是临床治疗骨质疏松症的候选药物之一。本研究利用GST基因融合系统表达重组人甲状旁腺素rP(HPTHrP)1-34和1-84。为了确定重组hPTHrP1-34和1-84是否可以促进肾钙重吸收和促进骨形成，我们检测了重组hPTHrP1-34和1-84在原代骨髓细胞培养体系中对成骨细胞系的作用以及在治疗骨质疏松方面的作用。结果表明，重组hPTHrP1-34和1-84均能促进体外集落形成和成骨细胞分化及矿化，但重组hPTHrP1-84的作用略强于hPTHrP1-34。接下来，用去卵巢的方法建立骨质疏松动物模型(OVX)，检测两种重组体的体内活性。HPTHrP1-84通过上调肾钙转运蛋白的表达而升高血钙，从而刺激成骨细胞的骨形成。这些因素导致hPTHrP1-84治疗的OVX小鼠骨量增加，但不影响骨吸收。HPTHrP1-34处理的OVX小鼠没有明显的骨量变化，这可能至少部分地与hPTHrP1-34在体内的半衰期比hPTHrP1-84短有关。本研究提示，重组hPTHrP1-84比hPTHrP1-34能更有效地促进肾钙重吸收和促进体内骨形成。
Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP) is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP) 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX) to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.
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影响因子：
2.3
作者：
Miao D;Scutt A
通讯作者：
Scutt A
影响因子：
7.3
作者：
Chang W;Tu C;Chen TH;Bikle D;Shoback D
通讯作者：
Shoback D
甲状旁腺激素有助于调节乳钙含量，并与钙协同调节新生儿骨形成
影响因子：
4.8
作者：
Cao, Guofan;Gu, Zhen;Miao, Dengshun
通讯作者：
Miao, Dengshun
DOI：
10.1073/pnas.0306141101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Dvorak, MM;Siddiqua, A;Riccardi, D
通讯作者：
Riccardi, D
影响因子：
5.8
作者：
Baron, Roland;Hesse, Eric
通讯作者：
Hesse, Eric