Down-regulation of osteoblastic cell differentiation by epidermal growth factor receptor.
The role of epidermal growth factor receptors (EGF-R) in osteogenic cell differentiation was investigated using preosteoblastic MC3T3-E1 (MC3T3) cells and osteoblast-like ROS 17/2.8 (ROS) cells. When cultured in the presence of beta-glycerophosphate (GP) and ascorbic acid (AA), MC3T3 cells underwent spontaneous differentiation into osteoblasts which was confirmed as they expressed osteoblast markers such as alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteocalcin (OC). Interestingly, the number of EGF-binding sites decreased during their differentiation into osteoblasts, and the osteogenic protein-1 (OP-1) treatment, which accelerated their differentiation, lowered the number of EGF-binding sites even further. On the other hand, ROS cells with high expression levels of osteoblast markers and no EGF-R, after being transfected with human EGF-R cDNA (EROS cells), expressed numerous EGF-binding sites as well as EGF-R mRNA and protein; in the process, they ceased to express osteoblast markers, indicating their dedifferentiation into osteoprogenitor cells. Both MC3T3 and EROS cells showed increased cell growth in response to EGF, whereas ROS cells did not. These results imply that the EGF/EGF-R system in osteogenic cells has a crucial function in osteoblast phenotype suppression and osteogenic cell proliferation.
Chien
H H
HH
China Medical College School of Dentistry, Taichung, Taiwan.
Lin
W L
WL
Cho
M I
MI
D000469:Alkaline Phosphatase / Q000235:genetics; D001205:Ascorbic Acid / Q000494:pharmacology; D015152:Blotting, Northern; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000235:genetics; D014170:Transformation, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D005994:Glycerophosphates; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid