Development of the osteoblast phenotype: molecular mechanisms mediating osteoblast growth and differentiation.
Development of the osteoblast phenotype: molecular mechanisms mediating osteoblast growth and differentiation.
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发表时间：
1995
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通讯作者：
J. Lian;G. Stein
中科院分区：
文献类型：
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作者：
J. Lian;G. Stein
骨组织的形成涉及成骨细胞的多种活动。分子、生物化学、组织化学和超微结构方法的联合应用已经确定了成骨细胞表型发育的阶段，每个细胞亚群表现出与矿化骨细胞外基质（ECM）有序沉积相关的独特形态和功能特性。表达基因的峰值水平反映了成骨细胞生长和分化的成熟序列，其特征在于三个主要时期：增殖，ECM成熟和矿化。在过去的几年中，大量的新信息提供了深入了解的分子机制调节分化成骨细胞的发展和活动的基础。这些新概念将在理解骨组织细胞反应的背景下进行讨论。要考虑的是以下：1）由转录因子的选择性表达反映的成骨细胞的成熟阶段（例如，癌基因、细胞周期蛋白、同源结构域蛋白）和通过成骨细胞谱系提供分化信号的表型基因; 2）细胞外基质在介导成骨细胞生长和分化中的作用; 3）成骨细胞阶段对生理介质（例如，生长因子和激素）; 4）成骨细胞表型基因的发育调节表达和选择性反应由基因启动子中多个基础和增强子或抑制子序列的协同、协同和/或拮抗活性支持;和5）在转化的成骨细胞和骨肉瘤细胞中这些控制机制的失调。
The formation of bone tissue involves multiple activities of the osteoblast. The combined application of molecular, biochemical, histochemical and ultrastructural approaches has defined stages in the development of the osteoblast phenotype with each subpopulation of cells exhibiting unique morphologic and functional properties in relation to the ordered deposition of the mineralized bone extracellular matrix (ECM). Peak levels of expressed genes reflect a maturational sequence of osteoblast growth and differentiation characterized by three principal periods: proliferation, ECM maturation and mineralization. A plethora of new information in the past several years provides the basis for insight into molecular mechanisms regulating the development and activities of differentiating osteoblasts. These new concepts will be discussed within the context of understanding cellular responses of bone tissue. To be considered are the following: 1) maturational stages of the osteoblast reflected by the selective expression of transcription factors (e.g., oncogenes, cyclins, homeodomain proteins) and phenotypic genes that provide signals for differentiation through the osteoblast lineage; 2) role of the extracellular matrix in mediating osteoblast growth and differentiation; 3) osteoblast stage specific responses to physiologic mediators (e.g., growth factors and hormones); 4) the developmentally regulated expression and selective responses of osteoblast phenotypic genes are supported by cooperative, synergistic and/or antagonistic activities at multiple basal and enhancer or suppressor sequences in gene promoters; and 5) deregulation of these control mechanisms in transformed osteoblasts and osteosarcoma cells.