Osteogenic protein-1 enhances phenotypic expression in ROS 17/2.8 cells.
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.
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010641:Phenotype; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018016:Receptors, Parathyroid Hormone / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D010281:Parathyroid Hormone; D011506:Proteins; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D004247:DNA; D003513:Cycloheximide; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D013936:Thymidine