OP‐1 (BMP‐7) Affects mRNA Expression of Type I, II, X Collagen, and Matrix Gla Protein in Ossifying Long Bones In Vitro

OP‐1 (BMP‐7) Affects mRNA Expression of Type I, II, X Collagen, and Matrix Gla Protein in Ossifying Long Bones In Vitro
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OP-1 (BMP-7) 影响体外长骨骨化中 I、II、X 型胶原和基质 Gla 蛋白的 mRNA 表达

DOI:
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发表时间:
1997
影响因子:
6.2
通讯作者:
E. H. Burger
E. H. Burger
中科院分区:
医学1区
文献类型:
--
作者:
A. Haaijman;Rena N. D'Souza;A. Bronckers;S. Goei;E. H. Burger

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在长骨发育中,OP-1的调节作用是由发育中的小鼠后肢中OP-1配体和OP-1结合受体的局部相关表达提出的。OP-1在趾间间充质中表达,而OP-1结合受体在相邻的软骨膜中发现,OP-1配体和受体都存在于(前)肥大软骨细胞区。我们通过用rhOP-1处理胚胎小鼠跖骨的器官培养物来研究OP-1在长骨发育中的作用。用原位杂交和细胞增殖用[3H]胸苷和BrdU标记研究I,II,X型胶原和基质Gla蛋白(MGP)的mRNA表达模式。在骨骺软骨膜中,用40 ng/ml OP-1处理2天后增强细胞增殖,而6天处理导致表达从I型胶原转变为II型胶原mRNA。这支持了先前的组织化学发现,OP-1诱导软骨膜转变为软骨。在雏形的中心,OP-1抑制X型胶原mRNA的表达,表明软骨细胞肥大的抑制。在OP-1处理的雏形中,大面积表达MGP mRNA的细胞也表明了在肥大前软骨细胞阶段的分化停滞。我们得出结论,OP-1通过作用于软骨内骨化的两个步骤影响软骨细胞分化标志基因的表达。首先,细胞增殖增强,特别是在软骨膜中,细胞开始表达软骨细胞表型。第二,成熟软骨细胞向肥大软骨细胞的终末分化受到抑制。这些结果,结合胚胎中OP-1配体和BMP受体表达的已知模式,表明OP-1在软骨内骨化过程中的级联反应中发挥局部作用。
In long bone development, a regulating role of OP‐1 is suggested by the local correlated expression of both OP‐1 ligand and OP‐1 binding receptors in developing mouse hind limbs. OP‐1 is expressed in the interdigital mesenchyme, whereas OP‐1 binding receptors are found in the bordering perichondrium, and both OP‐1 ligand and receptors are present in the zone of (pre)hypertrophic chondrocytes. We investigated the role of OP‐1 in long bone development experimentally by treating organ cultures of embryonic mouse metatarsals with rhOP‐1. The mRNA expression patterns of type I, II, X collagen, and matrix Gla protein (MGP) were studied using in situ hybridization and cell proliferation using [3H]thymidine and BrdU labeling. In the epiphyseal perichondrium, treatment with 40 ng/ml OP‐1 enhanced cell proliferation after day 2, while 6‐day treatment caused a shift in expression from type I collagen to type II collagen mRNA. This supports previous histochemical findings that OP‐1 induced the transition of perichondrium into cartilage. In the center of the rudiment, OP‐1 inhibited the expression of type X collagen mRNA, indicating inhibition of chondrocyte hypertrophy. An arrest of differentiation at the prehypertrophic chondrocyte stage was also indicated by the large area of cells expressing MGP mRNA in the OP‐1–treated rudiments. We conclude that OP‐1 affected the expression of marker genes of chondrocyte differentiation by acting on two steps in endochondral ossification. First, cell proliferation was enhanced, particularly so in the perichondrium where cells started to express the chondrocyte phenotype. Second, the terminal differentiation of mature chondrocytes into hypertrophic chondrocytes was inhibited. These results, combined with the known pattern of OP‐1 ligand and BMP receptor expression in the embryo, suggest that OP‐1 plays a local role in the cascade of events during endochondral ossification.
发育过程中胚胎鸡胸骨中 X 型胶原蛋白 mRNA 水平的表达。
DOI: 10.1016/0006-291x(86)90342-6
发表时间: 1986
影响因子: 3.1
作者:
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通讯作者: Jimenez,SA
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发表时间: 1995-11-15
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DOI: --
发表时间: 1992-10
期刊: The Journal of biological chemistry
影响因子: --
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DOI: 10.1006/bbrc.1993.1973
发表时间: 1993-08-16
影响因子: 3.1
作者:
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