Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression of osteoblastic cells from G1 to S phase
Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression of osteoblastic cells from G1 to S phase
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DOI：
10.1074/jbc.m409846200
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发表时间：
2005-01-28
影响因子：
4.8
通讯作者：
Partridge, NC
中科院分区：
文献类型：
--
作者：
Qin, L;Li, X;Partridge, NC
甲状旁腺激素(PTH)在骨重建中起主要作用，如果每天服用，就有能力增加骨量。在体外，甲状旁腺素抑制成骨细胞系的生长，使其停滞在G期。在这里，我们证明甲状旁腺激素调节至少三个基因的表达，以实现以下诱导MAPK磷酸酶1(MKP-1)和P21(Cip1)的表达，并在mRNA和蛋白水平上降低细胞周期蛋白D1的表达。MKP-1的诱导导致细胞外信号调节蛋白激酶去磷酸化，从而导致细胞周期蛋白D1的减少。MKP-1过表达可使UMR细胞停滞于G(1)期。对这些基因的甲状旁腺激素调控机制进行了研究。最重要的是，甲状旁腺激素对这些基因在大鼠股骨干骺端原发海绵体内的表达也有相似的影响。对p21(Cip1)在骨中表达水平的分析表明，每天重复注射PTH使成骨细胞对连续的PTH处理更加敏感，这可能是PTH合成代谢功能的一个重要特征。综上所述，我们的数据表明，甲状旁腺素发挥其合成代谢作用的一个机制是阻止成骨细胞的细胞周期进程，从而促进其分化。
Parathyroid hormone (PTH) plays a major role in bone remodeling and has the ability to increase bone mass if administered daily. In vitro, PTH inhibits the growth of osteoblastic cell lines, arresting them in G, phase. Here, we demonstrate that PTH regulates the expression of at least three genes to achieve the following inducing expression of MAPK phosphatase 1 (MKP-1) and P21(Cip1) and decreasing expression of cyclin D1 at both mRNA and protein levels. The induction of MKP-1 causes the dephosphorylation of extracellular signal-regulated kinase and therefore the decrease in cyclin D1. Overexpression of MKP-1 arrests UMR cells in G(1) phase. The mechanisms involved in PTH regulation of these genes were studied. Most importantly, PTH administration produces similar effects on expression of these genes in rat femoral metaphyseal primary spongiosa. Analyses of p21(Cip1) expression levels in bone indicate that repeated daily PTH injections make the osteoblast more sensitive to successive PTH treatments, and this might be an important feature for the anabolic functions of PTH. In summary, our data suggest that one mechanism for PTH to exert its anabolic effect is to arrest the cell cycle progression of the osteoblast and hence increase its differentiation.