Anabolic or catabolic responses of MC3T3-E1 osteoblastic cells to parathyroid hormone depend on time and duration of treatment
Anabolic or catabolic responses of MC3T3-E1 osteoblastic cells to parathyroid hormone depend on time and duration of treatment
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DOI：
10.1359/jbmr.1999.14.9.1504
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发表时间：
1999-09-01
影响因子：
6.2
通讯作者：
Howard, GA
中科院分区：
文献类型：
--
作者：
Schiller, PC;D'Ippolito, G;Howard, GA
我们研究了长期（30天）培养MC3T3-E1细胞（小鼠成骨细胞分化模型）对甲状旁腺激素（PTH）的信号传导（cAMP）和合成代谢反应（细胞外基质矿化[ECM]）。PTH/PTH相关肽受体（PTH1R） mRNA的表达在早期被检测到，并在2周内保持相对稳定，在培养期的后半段观察到更高的水平。与相对稳定的PTH1R mRNA表达相比，cAMP对PTH的反应变化明显，第5天无反应，第10天有明显反应（与对照组相比为80倍），在剩余的培养期间，对PTH的反应仍然升高，刺激波动为30至80倍。观察PTH治疗达到体外ECM矿化的着色和持续时间，在第20天前开始持续PTH治疗，矿化程度下降。如果在第20天或之后开始持续PTH治疗，矿化不受影响。然而，如果在第20天开始治疗，然后在第25天停止治疗，则在第30天矿化增加5倍。这种矿化对间歇性甲状旁腺激素的反应在小鼠和人成骨细胞的原代培养中得到证实。这些数据为理解甲状旁腺激素的不同反应（合成代谢与分解代谢）提供了潜在的基础，并表明了合成代谢和分解代谢反应的发育时间差异。由于cAMP信号在这段时间内（10-30天）相对不变，腺苷酸环化酶的刺激仅部分模拟了PTH对矿化增加的影响，因此为了确定分化过程中短期PTH治疗的具体合成代谢反应，可能涉及其他信号通路。
We have investigated signaling (cAMP) and anabolic responses (mineralization of extracellular matrix [ECM]) to parathyroid hormone (PTH) in long-term (30 days) cultures of MC3T3-E1 cells, a murine model of osteoblast differentiation. Expression of PTH/PTH-related peptide receptor (PTH1R) mRNA is detected early and remains relatively constant for 2 weeks with somewhat higher levels observed during the second half of the culture period. In contrast to the relatively stable PTH1R mRNA expression, the cAMP response to PTH varies markedly with no response at day 5 and a marked response (80-fold versus control) by day 10, Responsiveness to PTH remains elevated with fluctuations of 30- to 80-fold stimulation throughout the remainder of the culture period.;The tinting and duration of PTH treatment to achieve in vitro mineralization of ECM was evaluated, When continuous PTH treatment was initiated before day 20, mineralization decreased. If continuous PTH treatment began on or after day 20, mineralization was unaffected. However, if treatment began on day 20 and then stopped on day 25, mineralization on day 30 was increased 5-fold. This mineralization response to intermittent PTH was confirmed in primary cultures of murine and human osteoblastic cells. These data provide a potential basis for understanding the differential responses to PTH (anabolic versus catabolic) and indicate the developmental temporal variance of anabolic and catabolic responses. Since cAMP signaling was relatively unchanged during this interval (day 10-30) and stimulation of adenylate cyclase only partially mimicked the PTH effect on increased mineralization, other signaling pathways are likely to be involved in order to determine the specific anabolic response to short-term PTH treatment during the differentiation process.