Abstract
Inflammatory bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. Osteoprotegerin (OPG) is a soluble osteoblast-derived protein that influences bone resorption by inhibiting osteoclast differentiation and activation. In the present study, we demonstrate that interleukin-1beta and tumor necrosis factor alpha induce OPG mRNA production and OPG secretion by osteoblast-like MG-63 cells. Maximum induction of OPG secretion by either cytokine requires activation of the p38 mitogen activated protein kinase (MAPK) pathway but neither the p42/p44 (ERK) nor the c-Jun N-terminal MAPK pathways. Induction of OPG mRNA by either cytokine is also p38 MAPK dependent. Taken together, these data indicate that cytokine-induced OPG gene expression and protein secretion are differentially regulated by specific MAP kinase signal transduction pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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Cytokines / physiology*
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation*
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Enzyme-Linked Immunosorbent Assay
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Glycoproteins / biosynthesis*
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Humans
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Inflammation
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Interleukin-1 / metabolism
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Signaling System
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Osteoblasts / metabolism
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Osteoclasts / metabolism
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Osteoprotegerin
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Protein Structure, Tertiary
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RNA / metabolism
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / biosynthesis*
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Receptors, Tumor Necrosis Factor
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Cytokines
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DNA, Complementary
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Glycoproteins
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Interleukin-1
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Osteoprotegerin
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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TNFRSF11B protein, human
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Tumor Necrosis Factor-alpha
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RNA
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases