Protein kinase C βII and δ/θ play critical roles in bone morphogenic protein-4-stimulated osteoblastic differentiation of MC3T3-E1 cells.
Bone morphogenic protein-4 (BMP-4), one of TGF-β superfamily, is involved in bone and cartilage development, specifically tooth and bone fracture repair. In the present study, the role of protein kinase C (PKC) was investigated in BMP-4-induced differentiation of osteoblast-like MC3T3-E1 cells. PKC inhibitor UCN-01 significantly attenuated the synthesis of osteocalcin, a marker of mature osteoblast phenotype, in a dose-dependent manner as well as blocked osteroblastic differentiation and mineralization in BMP-4-treated MC3T3-E1 cells. Also, UCN-01 suppressed vascular endothelial growth factor (VEGF) production in BMP-4-treated MC3T3-E1 cells. In addition, UCN-01 remarkably suppressed BMP-4-activated PKC βII and PKC δ/θ of PKC family proteins by Western blotting. Consistently, 2-dimensional electrophoresis (2-DE) immunoblotting revealed that UCN-01 inhibited the BMP-4-induced activation of PKC subfamilies in MC3T3-E1 cells. Taken together, our findings suggest that PKC βII and PKC δ/θ mediate BMP-4-induced osteoblastic differentiation.
Park
Ki Ho
KH
Department of Orthodontics Kyung-Hee University School of Dentistry, Seoul 130-701, Republic of Korea.
Han
Dong In
DI
Rhee
Yun-Hee
YH
Jeong
Soo-Jin
SJ
Kim
Sung-Hoon
SH
Park
Young Guk
YG
D016475:3T3 Cells; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D055415:Bone Morphogenetic Protein 4; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C054852:7-hydroxystaurosporine; C497259:Prkcd protein, mouse; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta; D019311:Staurosporine