Maturational disturbance of chondrocytes in Cbfa1-deficient mice
Maturational disturbance of chondrocytes in Cbfa1-deficient mice
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DOI：
10.1002/(sici)1097-0177(199904)214:4
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发表时间：
1999-04-01
影响因子：
2.5
通讯作者：
Komori, T
中科院分区：
文献类型：
--
作者：
Inada, M;Yasui, T;Komori, T
Cbfa1是一个属于矮小结构域基因家族的转录因子，在成骨过程中起着重要的作用，Cbfa1基因缺陷小鼠由于成骨细胞的成熟停滞而完全缺乏膜内和软骨内成骨，表明Cbfa1在成骨细胞分化中具有基础作用。但Cbfa1在软骨细胞中也有表达，且随着软骨细胞的成熟其表达逐渐增强，终末肥大软骨细胞广泛表达Cbfa1，Cbfa1在胚胎13.5天(E13.5)最早在肥大软骨细胞中表达，在E14.5-16.5天表达最为明显。在Cbfa1基因缺陷小鼠，其整个骨骼由软骨组成，软骨细胞分化受到干扰，在骨骼的限制性部分，包括胫骨、腓骨、桡骨和尺骨，软骨发生钙化。肥大软骨细胞表达X型胶原、Bmp6和Hedgehog，而骨桥蛋白、骨涎蛋白和胶原酶3不表达，表明它们在终末肥大软骨细胞中受到Cbfa1的直接调控，其余骨骼中软骨细胞分化严重障碍。PTH/PTHrP受体、Hedgehog、X型胶原和Bmp6在肱骨和股骨中未检测到表达，表明软骨细胞分化受阻于肥大前期软骨细胞，提示Cbfa1是软骨细胞分化的重要因素。Dev Dyn 1999；214：279-290。(C)1999年Wiley-Liss，Inc.
Cbfa1, a transcription factor that belongs to the runt-domain gene family, plays an essential role in osteogenesis, Cbfa1-deficient mice completely lacked both intramembranous and endochondral ossification, owing to the maturational arrest of osteoblasts, indicating that Cbfa1 has a fundamental role in osteoblast differentiation. However, Cbfa1 was also expressed in chondrocytes, and its expression was increased according to the maturation of chondrocytes, Terminal hypertrophic chondrocytes expressed Cbfa1 extensively, The significant expression of Cbfa1 in hypertrophic chondrocytes was first detected at embryonic day 13.5 (E13.5), and its expression in hypertrophic chondrocytes was most prominent at E14.5-16.5. In Cbfa1-deficient mice, whose entire skeleton was composed of cartilage, the chondrocyte differentiation was disturbed, Calcification of cartilage occurred in the restricted parts of skeletons, including tibia, fibula, radius, and ulna. Type X collagen, BMP6, and Indian hedgehog were expressed in their hypertrophic chondrocytes, However, osteopontin, bone sialoprotein, and collagenase 3 were not expressed at all, indicating that they are directly regulated by Cbfa1 in the terminal hypertrophic chondrocytes, Chondrocyte differentiation was severely disturbed in the rest of the skeleton. The expression of PTH/PTHrP receptor, Indian hedgehog, type X collagen, and BMP6 was not detected in humerus and femur, indicating that chondrocyte differentiation was blocked before prehypertrophic chondrocytes, These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation. Dev Dyn 1999;214:279-290. (C) 1999 Wiley-Liss, inc.