Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells.
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.
Thies
R S
RS
Genetics Institute, Cambridge, Massachusetts 02140.
Bauduy
M
M
Ashton
B A
BA
Kurtzberg
L
L
Wozney
J M
JM
Rosen
V
V
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D019485:Bone Morphogenetic Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D010641:Phenotype; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D019485:Bone Morphogenetic Proteins; D010281:Parathyroid Hormone; D011506:Proteins; D011994:Recombinant Proteins; D014316:Tritium; D015675:Osteocalcin; D004247:DNA; D003513:Cycloheximide; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D013936:Thymidine