Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by MG-63 cells

Biochem Biophys Res Commun. 2005 Apr 1;329(1):224-9. doi: 10.1016/j.bbrc.2005.01.122.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cytokines / physiology*
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation*
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / biosynthesis*
  • Humans
  • Inflammation
  • Interleukin-1 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteoprotegerin
  • Protein Structure, Tertiary
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Tumor Necrosis Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Cytokines
  • DNA, Complementary
  • Glycoproteins
  • Interleukin-1
  • Osteoprotegerin
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human
  • Tumor Necrosis Factor-alpha
  • RNA
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases