New roles and mechanism of action of BMP4 in postnatal tooth cytodifferentiation.
New roles and mechanism of action of BMP4 in postnatal tooth cytodifferentiation.
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DOI：
10.1016/j.bone.2010.02.024
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发表时间：
2010-06
期刊：
影响因子：
4.1
通讯作者：
Harris, S. E.
中科院分区：
文献类型：
--
作者：
Gluhak-Heinrich, J.;Guo, D.;Yang, W.;Harris, M. A.;Lichtler, A.;Kream, B.;Zhang, J.;Feng, J. Q.;Smith, L. C.;Dechow, P.;Harris, S. E.
在小鼠出生后发生的明显牙齿细胞分化阶段，使用 3.6Collagen1a-Cre、BMP4 floxed 和 BMP4 敲除小鼠，出生后第 1 天左右产生早期胶原蛋白的成牙本质细胞中的 BMP4 基因被删除。牙槽成骨细胞和成牙本质细胞中的 BMP4 表达降低了 90% 以上。前牙本质到牙本质形成的速率降低，成熟成牙本质细胞分化减少，这反映在 DMP1 表达和正常牙本质小管形成的减少，以及 I 型胶原和骨钙蛋白表达的减少。我们观察到突变的畸形成牙本质细胞无法正常伸长和分化。这种失败的分化过程的后果是导致 10-12 个月大的小鼠牙本质厚度永久性丧失、臼齿牙髓腔明显增大以及支撑牙齿结构的骨量减少。成牙本质细胞中 BMP4 基因的缺失也间接破坏了终生持续的牙釉质形成过程。在成牙本质细胞中缺乏 BMP4 基因的情况下，这种分化程序改变的机制是由于 BMP 信号传导减少以及三个关键转录因子 Dlx3、Dlx5 和 Osterix 的表达减少。在成牙本质细胞 BMP4 cKO 小鼠的成釉细胞中，BMP 信号传导以及 Dlx3 和 Amelogenin 表达也间接减少。这支持了成牙本质细胞衍生的 BMP4 在出生后对正常的牙釉质生成和牙釉质形成的关键旁分泌或内分泌作用。
During the phase of overt tooth cytodifferentiation that occurs after birth in the mouse and using the 3.6Collagen1a-Cre, the BMP4 floxed and BMP4 knock-out mice, the BMP4 gene was deleted in early collagen producing odontoblasts around postnatal day 1. BMP4 expression was reduced over 90% in alveolar osteoblasts and odontoblasts. There was decreased rate of predentin to dentin formation and decreased mature odontoblast differentiation reflected in reduced DMP1 expression and proper dentinal tubule formation, as well as reduced Collagen type I and Osteocalcin expression. We observed mutant dysmorphogenic odontoblasts that failed to properly elongate and differentiate. The consequence of this failed differentiation process lead to permanent loss of dentin thickness, apparent enlarged pulp chambers in the molars and reduced bone supporting the tooth structures in mice as old as 10–12 months. Deletion of the BMP4 gene in odontoblasts also indirectly disrupted the process of enamel formation that persisted throughout life. The mechanism for this altered differentiation program in the absence of the BMP4 gene in odontoblasts is from decreased BMP signaling, and decreased expression of three key transcription factors, Dlx3, Dlx5, and Osterix. BMP signaling, as well as Dlx3 and Amelogenin expression, are also indirectly reduced in the ameloblasts of the odontoblast BMP4 cKO mice. This supports a key paracrine or endocrine role of odontoblasts derived BMP4 postnatally on the proper amelogenesis and formation of the enamel.
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影响因子：
7.6
作者：
Feng, JQ;Zhang, J;Harris, SE
通讯作者：
Harris, SE
影响因子：
64.5
作者：
VAINIO, S;KARAVANOVA, I;THESLEFF, I
通讯作者：
THESLEFF, I
影响因子：
1.5
作者：
Kulessa, H;Hogan, BLM
通讯作者：
Hogan, BLM
影响因子：
0.7
作者：
Liu, F;Woitge, HW;Kream, BE
通讯作者：
Kream, BE
影响因子：
2
作者：
Wright, J. Timothy;Hong, Sung P.;Luder, Hans U.
通讯作者：
Luder, Hans U.