Expression of cell cycle regulatory factors in differentiating osteoblasts: postproliferative up-regulation of cyclins B and E.
Expression of cell cycle regulatory factors in differentiating osteoblasts: postproliferative up-regulation of cyclins B and E.
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发表时间：
1995-11
期刊：
影响因子：
11.2
通讯作者：
Elisheva Smith;Baruch Frenkel;Robert Schlegel;Antonio Giordano;J. Lian;J. Stein;G. S. Stein
中科院分区：
文献类型：
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作者：
Elisheva Smith;Baruch Frenkel;Robert Schlegel;Antonio Giordano;J. Lian;J. Stein;G. S. Stein
在正常二倍体大鼠颅骨成骨细胞培养物中骨细胞表型的渐进发育过程中，分析了细胞周期蛋白和细胞周期蛋白依赖性激酶（cdks）的表现。检查了三个发育阶段：（a）增殖； (b) 单层汇合度； (c)骨细胞外基质的矿化。我们证明细胞周期蛋白和 cdks 的存在并不限于增殖期。与它们在细胞周期进展中的作用一致，cdc2 和 cdk2 在增殖后减少。然而，cdk4 和细胞周期蛋白 A、B 和 D1 持续存在于汇合细胞中。 Cyclin E 在细胞外基质矿化发育期间显着上调。对这些细胞周期调节蛋白的细胞质水平的检查表明细胞周期蛋白 B 在分化后期显着增加。在不支持分化的培养条件下维持的成骨细胞中未观察到核细胞周期蛋白 E 和细胞质细胞周期蛋白 B 的升高。此外，在增殖期用转化生长因子β处理48小时使细胞无法分化，并消除增殖后细胞周期蛋白B和E的上调。与增殖期相比，密度诱导的ROS 17/2.8骨肉瘤细胞的生长抑制不伴随核细胞周期蛋白E和细胞质细胞周期蛋白B的上调。这一观察结果与肿瘤细胞中生长控制和分化调节机制的废除是一致的。这些结果表明细胞周期调节蛋白不仅在增殖过程中发挥作用，而且可能在正常二倍体成骨细胞分化中发挥作用。
The representation of cyclins and cyclin-dependent kinases (cdks) was analyzed during progressive development of the bone cell phenotype in cultures of normal diploid rat calvarial osteoblasts. Three developmental stages were examined: (a) proliferation; (b) monolayer confluency; and (c) mineralization of the bone extracellular matrix. We demonstrate that the presence of cyclins and cdks is not restricted to the proliferation period. Consistent with their role in cell cycle progression, cdc2 and cdk2 decrease postproliferatively. However, cdk4 and cyclins A, B, and D1 persist in confluent cells. Cyclin E is significantly up-regulated during the extracellular matrix mineralization developmental period. Examination of the cytoplasmic levels of these cell cycle regulatory proteins indicates a marked increase in cyclin B in the late differentiation stage. The elevation of nuclear cyclin E and cytoplasmic cyclin B is not observed in osteoblasts maintained under culture conditions that do not support differentiation. Furthermore, treatment with transforming growth factor beta for 48 h during the proliferation period renders the cells incompetent for differentiation and abrogates the postproliferative up-regulation of cyclins B and E. Density-induced growth inhibition of ROS 17/2.8 osteosarcoma cells is not accompanied by up-regulation of nuclear cyclin E and cytoplasmic cyclin B when compared to the proliferation period. This observation is consistent with abrogation of both growth control and differentiation regulatory mechanisms in tumor cells. These results suggest that cell cycle regulatory proteins function not only during proliferation but may also play a role in normal diploid osteoblast differentiation.