OP-1 (BMP-7) affects mRNA expression of type 1, II, X collagen, and matrix Gla protein in ossifying long bones in vitro
OP-1 (BMP-7) affects mRNA expression of type 1, II, X collagen, and matrix Gla protein in ossifying long bones in vitro
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DOI：
10.1359/jbmr.1997.12.11.1815
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发表时间：
1997-11-01
影响因子：
6.2
通讯作者：
Burger, EH
中科院分区：
文献类型：
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作者：
Haaijman, A;DSouza, RN;Burger, EH
在长骨发育中，OP-1配体和OP-1结合受体在发育中的小鼠后肢局部相关表达，OP-1在指间充质中表达，而OP-1结合受体在邻近软骨膜中表达，OP-1配体和受体均存在于(前)肥大软骨细胞区。本研究通过实验探讨OP-1在长骨发育过程中的作用，采用原位杂交和[H-3]胸腺嘧啶核苷及BrdU标记细胞增殖的方法，研究了OP-1在长骨发育中的作用，并用[H-3]胸腺嘧啶核苷和BrdU标记，观察了OP-1诱导骨膜向软骨转化的组织化学结果。OP-1对软骨细胞分化的影响可能与OP-1对软骨细胞分化的影响有关。OP-1抑制软骨细胞肥大过程中X型胶原基因的表达，提示OP-1抑制了软骨细胞肥大前期的分化。OP-1作用于软骨细胞分化的两个阶段，提示OP-1通过作用于软骨内成骨的两个阶段而影响软骨细胞分化的标志基因的表达。首先，细胞增殖被促进，尤其是在细胞开始表达软骨细胞表型的软骨膜，其次，成熟软骨细胞向肥大软骨细胞的终末分化被抑制，这些结果结合已知的OP-1配体和BMP受体在胚胎中的表达模式，表明OP-1在软骨内成骨的一系列事件中起着局部作用。
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 [H-3]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-l 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.