The large functional spectrum of the heparin-binding cytokines MK and HB-GAM in continuously growing organs: The rodent incisor as a model

The large functional spectrum of the heparin-binding cytokines MK and HB-GAM in continuously growing organs: The rodent incisor as a model
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DOI:
10.1016/j.ydbio.2008.05.530
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发表时间:
2008-08-01
影响因子:
2.7
通讯作者:
Bluteau, Gilles
Bluteau, Gilles
中科院分区:
生物学3区
文献类型:
--
作者:
Mitsiadis, Thimios A.;Caton, Javier;Bluteau, Gilles

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肝素结合分子MK和HB-GAM参与调节多种组织器官的生长和分化。在这里,我们分析了MK和HB-GAM在发育中的小鼠切牙中的表达,这些切牙是具有干细胞室的持续生长的器官。MK和HB-GAM在切牙发育的所有阶段(起始、形态发生、细胞分化)都有重叠但不同的表达模式。这两种蛋白都在釉质结和颈环中检测到,釉质结是一种对牙齿形态发生至关重要的瞬时上皮信号结构,在牙齿外植体和器官型培养龛中研究干细胞MK和HB-GAM的功能。在试管中。在间充质外植体中,MK刺激HB-GAM的表达,反之亦然,HB-GAM上调MK的表达,从而表明这些蛋白之间存在一个调节环。骨形态发生蛋白和成纤维细胞生长因子分子也能激活间充质中两种细胞因子的表达。MK和HB-GAM的增殖作用因组织上皮源性间质的不同而不同。MK中和抗体对切牙胚芽的生长、细胞分化和矿化均有抑制作用。这些结果表明,MK和HB-GAM参与了小鼠切牙发育过程中干细胞的维持、细胞分化和矿化过程。(C)2008 Elsevier Inc.保留所有权利。
The heparin binding molecules MK and HB-GAM are involved in the regulation of growth and differentiation of many tissues and organs. Here we analyzed the expression of MK and HB-GAM in the developing mouse incisors, which are continuously growing organs with a stem cell compartment. Overlapping but distinct expression patterns for MK and HB-GAM were observed during all stages of incisor development (initiation, morphogenesis, cytodifferentiation). Both proteins were detected in the enamel knot, a transient epithelial signaling Structure that is important for tooth morphogenesis, and the cervical loop where the stem cell The functions of MK and HB-GAM were studied in dental explants and organotypic cultures niche is located. in vitro. in mesenchymal explants, MK stimulated HB-GAM expression and, vice-versa, HB-GAM upregulated MK expression, thus indicating a regulatory loop between these proteins. BMP and FGF molecules also activated expression of both cytokines in mesenchyme. The proliferative effects of MK and HB-GAM varied according to the mesenchymal OF epithelial Origin of the tissue. Growth, cytodifferentiation and mineralization were inhibited in incisor germs cultured in the presence of MK neutralizing antibodies. These results demonstrate that MK and HB-GAM are involved in stem cells maintenance, cytodifferentiation and mineralization processes during mouse incisor development. (C) 2008 Elsevier Inc. All rights reserved.