Kitten A M, Lee J C, Olson M S
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760, USA.
Am J Physiol. 1995 Nov;269(5 Pt 1):E918-26. doi: 10.1152/ajpendo.1995.269.5.E918.
Osteogenic protein-1 (OP-1) stimulates bone morphogenesis in vivo and modulates osteoblast growth and differentiation in vitro. Treatment of ROS 17/2.8 cells with OP-1 resulted in a time- and concentration-dependent inhibition of [3H]thymidine incorporation. In contrast, OP-1 treatment stimulated phenotypic differentiation in ROS 17/2.8 cells, as indicated by enhanced 1) alkaline phosphatase activity (4-fold); 2) alkaline phosphatase mRNA (5-fold); 3) parathyroid hormone receptor mRNA (2-fold), and 4) parathyroid hormone-stimulated adenosine 3',5'-cyclic monophosphate accumulation (2-fold). OP-1-induced changes in cell growth and gene expression were sensitive to cycloheximide and actinomycin D. Measurement of [3H]thymidine incorporation and alkaline phosphatase activity in situ revealed heterogeneity in the cellular responses to OP-1. Proliferating cells exhibited less alkaline phosphatase activity than nonproliferating cells, whereas cells expressing high levels of alkaline phosphatase incorporated little [3H]thymidine. Our data delineating the responses of mature differentiated osteoblasts to OP-1 suggest that potentiation of osteoblast differentiated function is an important component of bone morphogenesis in vivo.
成骨蛋白-1（OP-1）在体内刺激骨形态发生，在体外调节成骨细胞的生长和分化。用OP-1处理ROS 17/2.8细胞导致[3H]胸苷掺入呈时间和浓度依赖性抑制。相反，OP-1处理刺激了ROS 17/2.8细胞的表型分化，表现为：1）碱性磷酸酶活性增强（4倍）；2）碱性磷酸酶mRNA增加（5倍）；3）甲状旁腺激素受体mRNA增加（2倍）；4）甲状旁腺激素刺激的3',5'-环磷酸腺苷积累增加（2倍）。OP-1诱导的细胞生长和基因表达变化对放线菌酮和放线菌素D敏感。原位测量[3H]胸苷掺入和碱性磷酸酶活性揭示了细胞对OP-1反应的异质性。增殖细胞的碱性磷酸酶活性低于非增殖细胞，而表达高水平碱性磷酸酶的细胞掺入的[3H]胸苷很少。我们关于成熟分化成骨细胞对OP-1反应的数据表明，增强成骨细胞分化功能是体内骨形态发生的一个重要组成部分。
