Temporal and spatial expression of a growth-regulated network of imprinted genes in growth plate

Temporal and spatial expression of a growth-regulated network of imprinted genes in growth plate
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DOI:
10.1007/s00467-009-1339-y
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发表时间:
2010-04-01
影响因子:
3
通讯作者:
Nilsson, Ola
Nilsson, Ola
中科院分区:
医学3区
文献类型:
--
作者:
Andrade, Anenisia C.;Lui, Julian C.;Nilsson, Ola

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在哺乳动物中,躯体生长速度在胎儿和产后早期迅速,然后逐渐下降并最终停止。为了寻找导致多组织协调生长减速的基本生物学机制,最近发现了一个基于出生后生长过程中几个器官表达协调下降的印迹基因网络。为了探索其在纵向骨生长中的可能作用,我们利用实时荧光定量PCR技术对1、3和9周龄大鼠的微解剖干骺端骨和生长板区出生后生长过程中该网络的表达进行了表征。在生长板中修饰网络的表达模式。与之前在肾、肺、肝和心脏中观察到的协同下降类似,除Gtl2外,干骺骨中所有基因的表达都随着年龄的增长而下降。相反,随着生长板年龄的增长,Mest、Dlk1、H19、Gtl2降低,Cdkn1c、Grb10、Slc38a4升高。在静息区向肥厚区分化过程中,Mest、Dlk1、Grb10和Gtl2的表达减少,而Slc38a4的表达增加。特别是生长促进基因Mest、Dlk1、Gtl2和生长抑制基因Cdkn1c和Grb10表达的发育变化可能导致纵向骨生长随着年龄的增长而下降。
In mammals, the somatic growth rate is rapid during fetal and early postnatal life and then gradually declines and eventually stops. In search of the fundamental biological mechanism causing coordinated growth deceleration in multiple tissues, a network of imprinted genes was recently identified based on a coordinated decline in expression in several organs during postnatal growth. To explore a possible role in longitudinal bone growth, we characterized expression of the network during postnatal growth in microdissected metaphyseal bone and growth plate zones of 1-, 3-, and 9-week-old rats using real-time PCR. The expression pattern of the network is modified in growth plate. Similar to the coordinated decline previously observed in kidney, lung, liver, and heart, expression of all genes, except Gtl2, decreased with age in metaphyseal bone. On the contrary, Mest, Dlk1, H19, and Gtl2 decreased, and Cdkn1c, Grb10, and Slc38a4 increased with age in growth plate. During differentiation from resting to hypertrophic zone, Mest, Dlk1, Grb10, and Gtl2 expression decreased, whereas Slc38a4 expression increased. In particular, developmental changes in the expression of growth-promoting genes, Mest, Dlk1, Gtl2, and growth-inhibitory genes, Cdkn1c and Grb10, may contribute to the decline in longitudinal bone growth that occurs with age.