ABERRANT GENE-EXPRESSION IN CULTURED MAMMALIAN BONE-CELLS DEMONSTRATES AN OSTEOBLAST DEFECT IN OSTEOPETROSIS
ABERRANT GENE-EXPRESSION IN CULTURED MAMMALIAN BONE-CELLS DEMONSTRATES AN OSTEOBLAST DEFECT IN OSTEOPETROSIS
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DOI：
10.1002/jcb.240550314
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发表时间：
1994-07-01
影响因子：
4
通讯作者：
MARKS, SC
中科院分区：
文献类型：
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作者：
JACKSON, ME;SHALHOUB, V;MARKS, SC
石骨症是一种骨骼疾病，其中骨的普遍不透射线性是由破骨细胞对骨的吸收减少引起的。然而，最近的研究表明，在骨骼发育过程中，在几个骨硬化大鼠突变的基因表达中发生特异性畸变，反映了骨形成细胞、成骨细胞和组织组织发育的活性。为了评估其发病的意义，在体外研究了成骨细胞的渐进分化。正常成骨细胞的原代培养物经历与骨骼组织发育相关的细胞生长和组织相关基因的顺序表达。我们报告说，成骨细胞培养可以建立从这些突变体之一，无牙;这些细胞在体外表现出类似的畸变，在细胞增殖和细胞外基质形成和矿化过程中观察到的基因表达在体内;和一个加速成熟序列的突变成骨细胞模仿这种疾病的特征性骨骼硬化症。这些数据是第一个直接的证据，内在成骨细胞缺陷的石骨症，并建立了一个体外模型的遗传性骨骼疾病的研究。(C)1994 Wiley-Liss，Inc.
Osteopetrosis is a skeletal condition in which a generalized radioopacity of bone is caused by reduced resorption of bone by osteoclasts. However, it has recently been shown that during skeletal development in several osteopetrotic rat mutations specific aberrations occur in gene expression reflecting the activity of the bone forming cells, osteoblasts, and the development of tissue organization. To evaluate their pathogenetic significance, progressive osteoblast differentiation was studied in vitro. Primary cultures of normal osteoblasts undergo a sequential expression of cell growth and tissue-related genes associated with development of skeletal tissue. We report that osteoblast cultures can be established from one of these mutants, toothless; that these cells in vitro exhibit similar aberrations in gene expression during cell proliferation and extracellular matrix formation and mineralization observed in vivo; and that an accelerated maturation sequence by mutant osteoblasts mimics the characteristic skeletal sclerosis of this disease. These data are the first direct evidence for an intrinsic osteoblast defect in osteopetrosis and establish an in vitro model for the study of heritable skeletal disorders. (C) 1994 Wiley-Liss, Inc.