PLEIOTROPIC EFFECTS OF VITAMIN-D ON OSTEOBLAST GENE-EXPRESSION ARE RELATED TO THE PROLIFERATIVE AND DIFFERENTIATED STATE OF THE BONE CELL PHENOTYPE - DEPENDENCY UPON BASAL LEVELS OF GENE-EXPRESSION, DURATION OF EXPOSURE, AND BONE-MATRIX COMPETENCE IN NORMAL RAT OSTEOBLAST CULTURES
PLEIOTROPIC EFFECTS OF VITAMIN-D ON OSTEOBLAST GENE-EXPRESSION ARE RELATED TO THE PROLIFERATIVE AND DIFFERENTIATED STATE OF THE BONE CELL PHENOTYPE - DEPENDENCY UPON BASAL LEVELS OF GENE-EXPRESSION, DURATION OF EXPOSURE, AND BONE-MATRIX COMPETENCE IN NORMAL RAT OSTEOBLAST CULTURES
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DOI：
10.1210/endo-128-3-1496
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发表时间：
1991-03-01
期刊：
影响因子：
4.8
通讯作者：
LIAN, JB
中科院分区：
文献类型：
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作者：
OWEN, TA;ARONOW, MS;LIAN, JB
培养的正常大鼠成骨细胞经历一个发育序列，包括增殖期，其中高水平的组蛋白和I型胶原基因表达，随后是基质成熟期[高水平的碱性磷酸酶（AP）]和矿化期，这表明骨桥蛋白（OP）和骨钙素（OC）的高水平产生。 由于这些参数由维生素D调节，因此在成骨细胞生长和分化期间检查了用1，25-二羟基维生素D3短期和长期治疗的效果。 在急性研究中，在增殖期，组蛋白mRNA（反映DNA合成）被抑制（20-60%）。 基质Gla蛋白（MGP）和OP的mRNA显着升高增殖过程中（30和15倍），在相反的OC不表达，不诱导激素治疗。 OP和MGP在整个发育过程中仍然受到刺激，但程度较低（6至10倍）。 胶原蛋白和AP mRNA的抑制激素在其表达的峰值水平，但在矿化期刺激其最低的基础水平。 OC的表达，这是在矿化开始时启动，刺激13- 15倍时，基础水平低，然后从6- 8倍，激素在整个表达期间。 在慢性研究中，观察到不同的基因表达谱。 当激素治疗开始在第6天的增殖期，I型胶原和AP的表达受到抑制，矿化结节没有发展，OP和OC基因表达的诱导水平没有发生。 当慢性治疗开始后第20天的发展矿化基质，OC，但不是胶原蛋白和OP，水平刺激的激素。 这一观察结果与OC表达所需的活性或矿化骨基质一致。 与此相反，MGP的表达刺激慢性维生素D治疗的文化类似的急性治疗。 总之，这些研究表明，维生素D，骨形成和重塑的生理介质，可以积极和消极地调节成骨细胞表型标志物的表达作为激素治疗的持续时间和基因表达的基础水平的函数，这是骨基质能力和成骨细胞的分化状态的反映。
Normal rat osteoblasts in culture undergo a developmental sequence consisting of a proliferation period in which high levels of the histone and collagen type I genes are expressed, followed by periods of matrix maturation [high levels of alkaline phosphatase (AP)] and minerlization that signal a high level of production of osteopontin (OP) and osteocalcin (OC). Since these parameters are regulated by vitamin D, the effects of both short term and chronic treatment with 1,25-dihydroxyvitamin D3 were examined during osteoblast growth and differentiation. In acute studies, during the proliferation period, histone mRNA (reflecting DNA synthesis) was inhibited (20-60%). Matrix Gla protein (MGP) and OP mRNA were significantly elevated during proliferation (30- and 15-fold), in contrast to OC which is not expressed and was not induced by hormone treatment. OP and MGP remained stimulated throughout the developmental sequence, but to a lesser degree (from 6- to 10-fold). Collagen and AP mRNA were inhibited by hormone at their peak levels of expression, but were stimulated at their lowest basal levels in the mineralization period. OC expression, which was initiated at the onset of mineralization, was stimulated 13- to 15-fold when basal levels were low, then from 6- to 8-fold by hormone throughout its period of expression. In chronic studies a different profile of gene expression was observed. When hormone treatment was initiated during the proliferation period on day 6, type I collagen and AP expression were suppressed, mineralized nodules did not develop, and induced levels of OP and OC gene expression did not occur. When chronic treatment was initiated on day 20 after the development of a mineralized matrix, OC, but not collagen and OP, levels were stimulated by the hormone. This observation is consistent with the requirement of a competent or mineralized bone matrix for expression of OC. In contrast, MGP expression was stimulated in the chronic vitamin D-treated cultures similar to acute treatments. Taken together these studies demonstrate that vitamin D, a physiological mediator of bone formation and remodelling, can both positively and negatively regulate expression of osteoblast phenotypic markers as a function of duration of hormone treatment and basal levels of gene expression, which is a reflection of bone matrix competency and the differentiated state of the osteoblast.