Dual functional roles of dentin matrix protein 1 -: Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store
Dual functional roles of dentin matrix protein 1 -: Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store
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DOI：
10.1074/jbc.m212700200
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发表时间：
2003-05-09
影响因子：
4.8
通讯作者：
George, A
中科院分区：
文献类型：
--
作者：
Narayanan, K;Ramachandran, A;George, A
牙本质基质蛋白1 （DMP1）是一种骨和牙齿特异性蛋白，最初从矿化牙本质中发现。在这里，我们报道DMP1主要定位于未分化成骨细胞的核室。在细胞核中，DMP1作为成骨细胞特异性基因（如骨钙素）激活的转录成分。在成骨细胞成熟的早期阶段，Ca2+从细胞质涌入细胞核，通过酪蛋白激酶II的核异构体触发DMP1的磷酸化。磷酸化的DMP1随后被输出到细胞外基质，在那里它调节羟基磷灰石的成核。因此，DMP1是一种独特的分子，通过细胞核内的转录启动成骨细胞分化，并在成骨细胞成熟的后期协调细胞外矿化基质的形成。这里提供的数据代表了对DMP1功能理解的范式转变。这些信息对于理解正常骨形成、重塑、骨折愈合和骨骼组织修复至关重要。
Dentin matrix protein 1 (DMP1) is a bone- and teeth-specific protein initially identified from mineralized dentin. Here we report that DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca2+ surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. Thus, DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The data presented here represent a paradigm shift in the understanding of DMP1 function. This information is crucial in understanding normal bone formation, remodeling, fracture healing, and skeletal tissue repair.