Thies R S, Bauduy M, Ashton B A, Kurtzberg L, Wozney J M, Rosen V
Genetics Institute, Cambridge, Massachusetts 02140.
Endocrinology. 1992 Mar;130(3):1318-24. doi: 10.1210/endo.130.3.1311236.
To better understand the in vivo bone-inductive properties of recombinant human (rh) BMP-2, we examined the ability of the protein to alter the phenotype of a bone marrow stromal cell line. W-20-17. rhBMP-2 increased alkaline phosphatase activity in W-20-17 cells in a dose-responsive manner in the absence of an effect on proliferation. The induction of alkaline phosphatase activity was not apparent until 12 h after rhBMP-2 treatment had begun and was effectively eliminated by cotreatment with cycloheximide, suggesting a requirement for protein synthesis. Continued treatment of W-20-17 cells with rhBMP-2 for 8 days resulted in a significant increase, compared to control cultures, in the production of cellular cAMP in response to a PTH challenge. In addition, 4-day treatment with rhBMP-2 induced osteocalcin levels in W-20-17 cells. These results indicate that rhBMP-2 induces the expression of several markers associated with the osteoblast phenotype in W-20-17 cells and raises the possibility that BMP-2 may be involved in the differentiation of osteoblasts from progenitor cells resident in bone marrow.
为了更好地理解重组人（rh）骨形态发生蛋白-2（BMP-2）的体内骨诱导特性，我们检测了该蛋白改变骨髓基质细胞系W-20-17表型的能力。rhBMP-2以剂量依赖方式增加W-20-17细胞中的碱性磷酸酶活性，且对细胞增殖无影响。rhBMP-2处理开始12小时后碱性磷酸酶活性的诱导才明显，且用环己酰亚胺共处理可有效消除这种诱导，提示需要蛋白质合成。与对照培养物相比，用rhBMP-2持续处理W-20-17细胞8天导致细胞对甲状旁腺激素（PTH）刺激产生的环磷酸腺苷（cAMP）显著增加。此外，用rhBMP-2处理4天可诱导W-20-17细胞中的骨钙素水平。这些结果表明，rhBMP-2诱导W-20-17细胞中与成骨细胞表型相关的几种标志物的表达，并增加了BMP-2可能参与骨髓中祖细胞向成骨细胞分化的可能性。
