Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells

Autor: Sergio Roman-Roman, François Lallemand, Sylvie Gallea, Chi Faucheu, Georges Rawadi, L Huet, Shinji Kawai, S Spinella-Jaegle, Valerie Ramez, Azeddine Atfi, Roland Baron
Rok vydání: 2001
Předmět:
musculoskeletal diseases
medicine.medical_specialty
Histology
Physiology
MAP Kinase Signaling System
Pyridines
Endocrinology
Diabetes and Metabolism
Cellular differentiation
MAP Kinase Kinase 3
Osteocalcin
Bone Morphogenetic Protein 2
Biology
Mitogen-activated protein kinase kinase
Bone morphogenetic protein
Bone morphogenetic protein 2
p38 Mitogen-Activated Protein Kinases
Gene Expression Regulation
Enzymologic
Mice
Transforming Growth Factor beta
Internal medicine
Cricetinae
medicine
Animals
Mitogen-Activated Protein Kinase 8
RNA
Messenger
Enzyme Inhibitors
Protein kinase A
Cells
Cultured
Flavonoids
Mitogen-Activated Protein Kinase Kinases
Bone Development
Osteoblasts
Stem Cells
Imidazoles
Osteoblast
Cell Differentiation
Transforming growth factor beta
Protein-Tyrosine Kinases
Alkaline Phosphatase
Cell biology
Bone morphogenetic protein 7
medicine.anatomical_structure
Endocrinology
Bone Morphogenetic Proteins
biology.protein
Female
Mitogen-Activated Protein Kinases
Zdroj: Bone. 28(5)
ISSN: 8756-3282
Popis: Bone morphogenetic protein (BMP)-2, a member of the transforming growth factor-beta (TGF-beta) superfamily, is able to induce osteoblastic differentiation of C2C12 cells. Both Smad and mitogen-activated protein kinase (MAPK) pathways are essential components of the TGF-beta superfamily signaling machinery. Although Smads have been demonstrated to participate in the BMP-2-induced osteoblastic differentiation of C2C12 cells, the role of MAPK has not been addressed. This report shows that BMP-2 activates ERK and p38, but not JNK, in C2C12 cells. Pretreatment of cells with the p38 inhibitor, SB203580, dramatically reduced BMP-2-induced expression of the osteoblast markers alkaline phosphatase (ALP) and osteocalcin (OC). Nevertheless, overexpression of MKK3, a protein kinase that phosphorylates and activates p38, failed to induce ALP or OC expression in the absence of BMP-2, indicating that p38 activation is necessary but not sufficient for the acquisition of the osteoblast phenotype by these cells. Although ALP induction was increased slightly in the presence of PD-98059, a selective inhibitor of the ERK cascade, this compound significantly inhibited both steady-state and BMP-2-induced OC RNA levels. Our results indicate that p38 and ERK cascades play a crucial role in the osteoblast differentiation of C2C12 cells mediated by BMP-2.
Databáze: OpenAIRE
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