PROGRESSION AND RECAPITULATION OF THE CHONDROCYTE DIFFERENTIATION PROGRAM - CARTILAGE MATRIX PROTEIN IS A MARKER FOR CARTILAGE MATURATION
PROGRESSION AND RECAPITULATION OF THE CHONDROCYTE DIFFERENTIATION PROGRAM - CARTILAGE MATRIX PROTEIN IS A MARKER FOR CARTILAGE MATURATION
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DOI：
10.1006/dbio.1995.0024
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发表时间：
1995-11-01
影响因子：
2.7
通讯作者：
GOETINCK, PF
中科院分区：
文献类型：
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作者：
CHEN, Q;JOHNSON, DM;GOETINCK, PF
在软骨内成骨过程中，长骨软骨基质中的软骨细胞经过空间和时间调控的分化程序，然后被骨取代。为了了解这一过程，我们对分化程序进行了表征，并分析了软骨细胞及其细胞外环境在该程序调控中的关系。我们的研究结果表明，在骨骺生长板中，增殖软骨细胞的区域与X型胶原基因转录鉴定的肥大软骨细胞区域不相邻。我们发现构成增生区和肥大区之间的增生后软骨细胞特异性地转录软骨基质蛋白（CMP）基因。这个区域被称为成熟区。这种独特的软骨细胞群的鉴定表明，软骨细胞分化程序包括至少三个阶段。CMP翻译产物存在于成熟区和肥大区非增殖性软骨细胞周围的基质中。因此，CMP是有丝分裂后软骨细胞的标志物。由于在分化过程中基因表达的变化，每个区域的软骨细胞驻留在具有独特大分子组成的细胞外基质中。原代细胞培养的软骨细胞可以进行与软骨雏形相同的分化程序。在培养中，分化的浪潮开始于一个群体的中心，并向其外围扩散。增殖停止与CMP的出现一致，最终细胞肥大并合成X型胶原蛋白。这些结果揭示了软骨细胞分化过程中增殖-成熟过渡和成熟-肥大过渡的不同开关，并表明随着分化的进行，软骨细胞合成新的基质分子，从而改变其原有的微环境。然而，当“终末”分化的肥大软骨细胞从周围环境中释放出来并在小球培养中孵育时，它们会停止X型胶原合成，恢复增殖，并重新启动聚集蛋白合成。最终，它们停止增殖并重新启动CMP合成，最终形成X型胶原。因此，它们能够在体外重现分化程序的所有三个阶段。这些数据表明，软骨细胞分化程序具有高度的可塑性，并证明该程序的进展和维持至少部分受到软骨内骨形成过程中围绕分化的软骨细胞的细胞外环境的调节。(C) 1995学术出版社，Inc。
During endochondral bone formation, chondrocytes in the cartilaginous anlage of long bones progress through a spatially and temporally regulated differentiation program before being replaced by bone. To understand this process, we have characterized the differentiation program and analyzed the relationship between chondrocytes and their extracellular environment in the regulation of the program. Our results indicate that, within an epiphyseal growth plate, the zone of proliferating chondrocytes is not contiguous with the zone of hypertrophic chondrocytes identified by the transcription of the type X collagen gene. We find that the postproliferative chondrocytes which make up the zone between the zones of proliferation and hypertrophy specifically transcribe the gene for cartilage matrix protein (CMP). This zone has been termed the zone of maturation. The identification of this unique population of chondrocytes demonstrates that the chondrocyte differentiation program consists of at least three stages. CMP translation products are present in the matrix surrounding the nonproliferative chondrocytes of both the zones of maturation and hypertrophy. Thus, CMP is a marker for postmitotic chondrocytes. As a result of the changes in gene expression during the differentiation program, chondrocytes in each zone reside in an extracellular matrix with a unique macromolecular composition. Chondrocytes in primary cell culture can proceed through the same differentiation program as they do in the cartilaginous rudiments. In culture, a wave of differentiation begins in the center of a colony and spreads to its periphery. The cessation of proliferation coincides with the appearance of CMP and eventually the cells undergo hypertrophy and synthesize type X collagen. These results reveal distinct switches at the proliferative-maturation transition and at the maturation-hypertrophy transition during chondrocyte differentiation and indicate that chondrocytes synthesize new matrix molecules and thus modify their preexisting microenvironment as differentiation progresses. However, when ''terminally'' differentiated hypertrophic chondrocytes are released from their surrounding environment and incubated in pellet culture, they stop type X collagen synthesis, resume proliferation, and reinitiate aggrecan synthesis. Eventually they cease proliferation and reinitiate CMP synthesis and finally type X collagen. Thus they are capable of recapitulating all three stages of the differentiation program in vitro. The data suggest a high degree of plasticity in the chondrocyte differentiation program and demonstrate that the progression and maintenance of this program is regulated, at least in part, by the extracellular environment which surrounds a differentiating chondrocyte during endochondral bone formation. (C) 1995 Academic Press, Inc.