Glucocorticoids Induce Rapid Up-Regulation of Mitogen-Activated Protein Kinase Phosphatase-1 and Dephosphorylation of Extracellular Signal-Regulated Kinase and Impair Proliferation in Human and Mouse Osteoblast Cell Lines

A central feature of glucocorticoid (GC)-induced osteoporosis is decreased bone formation, secondary to decreased numbers of functional osteoblasts. We find that ERK activity is essential for serum-induced osteoblast proliferation in vitro because inhibition of MAPK/ERK kinase activity by U0126 comp...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2003-02, Vol.144 (2), p.412-422
Main Authors: Engelbrecht, Y, de Wet, H, Horsch, K, Langeveldt, C. R, Hough, F. S, Hulley, P. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Proteins - pharmacology
Bone growth
Cell Cycle Proteins
Cell Division - drug effects
Cell Division - physiology
Cell Line
Cell lines
Cell proliferation
Cycloheximide
Cytosol - enzymology
Dephosphorylation
Dexamethasone
Dexamethasone - pharmacology
Down-Regulation - physiology
Dual Specificity Phosphatase 1
Extracellular signal-regulated kinase
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation, Enzymologic - drug effects
Genes, Immediate-Early - physiology
Glucocorticoids
Glucocorticoids - pharmacology
Hormone Antagonists - pharmacology
Humans
Immediate-Early Proteins - genetics
Immediate-Early Proteins - metabolism
Kinases
MAP kinase
MAP kinase phosphatase
Mice
Mifepristone - pharmacology
Mitogen-Activated Protein Kinases - metabolism
MKP-1 protein
Osteoblasts
Osteoblasts - cytology
Osteoblasts - enzymology
Osteogenesis
Osteoporosis
Phosphatase
Phosphoprotein Phosphatases
Phosphorylation
Protein biosynthesis
Protein folding
Protein Phosphatase 1
Protein synthesis
Protein Tyrosine Phosphatases - genetics
Protein Tyrosine Phosphatases - metabolism
Protein-tyrosine-phosphatase
Proteins
Real time
Skeleton and joints
Transcriptional Activation - drug effects
Tyrosine
Up-regulation
Up-Regulation - drug effects
Vanadate
Vanadates
Vertebrates: osteoarticular system, musculoskeletal system
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Summary:A central feature of glucocorticoid (GC)-induced osteoporosis is decreased bone formation, secondary to decreased numbers of functional osteoblasts. We find that ERK activity is essential for serum-induced osteoblast proliferation in vitro because inhibition of MAPK/ERK kinase activity by U0126 completely abolished both serum-induced activation of ERK and proliferation of mouse (MBA-15.4) and human (MG-63) osteoblast cell lines. Dexamethasone (Dex) rapidly (
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-220769