Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype
Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype
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DOI：
10.1074/jbc.m412911200
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发表时间：
2005-02-18
影响因子：
4.8
通讯作者：
Feng, JQ
中科院分区：
文献类型：
--
作者：
Ye, L;Mishina, Y;Feng, JQ
了解软骨形成调控的分子机制对了解胚胎骨发育和出生后骨生长的生理学至关重要。虽然对软骨形成中的生长因子信号传导有很多了解，但非胶原基质蛋白在这一过程中的调节作用仍然很大程度上未知。在目前的研究中，我们提出的证据表明，在出生后的软骨形成的关键作用的牙本质基质蛋白1（dentin matrix protein 1）。Dmp 1基因最初是从大鼠门牙cDNA文库中发现的，并已被证明在后期牙本质发生中发挥重要作用。尽管产前骨骼发育没有观察到明显异常，但Dmp 1缺陷（Dmp 1（-I-））小鼠在出生后软骨形成期间意外地出现了严重的软骨形成缺陷。Dmp 1缺陷（Dmp 1（-I-））小鼠的椎骨和长骨较短且较宽，具有延迟和畸形的次级骨化中心以及不规则和高度扩张的生长板，这是高度扩张的增殖和高度扩张的肥大区的结果，产生类似于侏儒症伴软骨发育不良的表型。这种表型似乎是由于增殖区的细胞增殖增加和肥大区的细胞凋亡减少。此外，Dmp 1（-I-）小鼠的骨骺血管侵袭受损。这些发现表明，DMP 1是必要的正常出生后软骨和随后的骨形成。
Understanding the molecular mechanisms by which cartilage formation is regulated is essential toward understanding the physiology of both embryonic bone development and postnatal bone growth. Although much is known about growth factor signaling in cartilage formation, the regulatory role of noncollagenous matrix proteins in this process are still largely unknown. In the present studies, we present evidence for a critical role of DMP1 (dentin matrix protein 1) in postnatal chondrogenesis. The Dmp1 gene was originally identified from a rat incisor cDNA library and has been shown to play an important role in late stage dentinogenesis. Whereas no apparent abnormalities were observed in prenatal bone development, Dmp1-deficient (Dmp1(-I-)) mice unexpectedly develop a severe defect in cartilage formation during postnatal chondrogenesis. Vertebrae and long bones in Dmp1-deficient (Dmp1(-I-)) mice are shorter and wider with delayed and malformed secondary ossification centers and an irregular and highly expanded growth plate, results of both a highly expanded proliferation and a highly expanded hypertrophic zone creating a phenotype resembling dwarfism with chondrodysplasia. This phenotype appears to be due to increased cell proliferation in the proliferating zone and reduced apoptosis in the hypertrophic zone. In addition, blood vessel invasion is impaired in the epiphyses of Dmp1(-I-) mice. These findings show that DMP1 is essential for normal postnatal chondrogenesis and subsequent osteogenesis.