Pediatric Endocrinology Unit and Center for Molecular Medicine, Q2:08, Department of Woman and Child Health, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden.
Pediatr Nephrol. 2010 Apr;25(4):617-23. doi: 10.1007/s00467-009-1339-y. Epub 2009 Nov 10.
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.
在哺乳动物中，胎儿期和出生后早期的体生长速度很快，然后逐渐下降，最终停止。为了寻找导致多种组织生长减速的基本生物学机制，最近根据出生后生长过程中几个器官表达的协同下降，确定了一组印迹基因网络。为了探索其在纵向骨生长中的可能作用，我们使用实时 PCR 技术，在 1 、 3 和 9 周龄大鼠的微分离骺骨和生长板区域中，对网络在出生后生长过程中的表达进行了特征描述。网络的表达模式在生长板中发生了改变。与先前在肾脏、肺、肝和心脏中观察到的协调下降相似，除 Gtl2 外，所有基因在骺骨中的表达均随年龄而降低。相反，在生长板中，Mest 、 Dlk1 、 H19 和 Gtl2 随年龄而降低，而 Cdkn1c 、 Grb10 和 Slc38a4 则随年龄而增加。从静止期到肥大期分化过程中，Mest 、 Dlk1 、 Grb10 和 Gtl2 的表达降低，而 Slc38a4 的表达增加。特别是促进生长的基因 Mest 、 Dlk1 、 Gtl2 和生长抑制基因 Cdkn1c 和 Grb10 的表达变化，可能有助于与年龄相关的纵向骨生长下降。
