Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells

Biochem Biophys Res Commun. 1998 Jul 30;248(3):454-7. doi: 10.1006/bbrc.1998.8993.


Osteoprotegerin (OPG) is a recently cloned soluble member of the tumor necrosis factor receptor family. OPG has been shown to inhibit osteoclast recruitment by binding to OPG-ligand, an osteoclast differentiating factor on osteoblastic stromal cells, thereby blocking osteoclastogenesis. In this report we have examined the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-alpha and TNF-beta dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-alpha and 1 pM of TNF-beta. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-alpha or TNF-beta. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms
  • Glycoproteins / biosynthesis*
  • Humans
  • Kinetics
  • Lymphotoxin-alpha / biosynthesis*
  • Osteoprotegerin
  • Osteosarcoma
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Receptors, Cytoplasmic and Nuclear*
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Time Factors
  • Transcription, Genetic / drug effects*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects


  • Glycoproteins
  • Lymphotoxin-alpha
  • Osteoprotegerin
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human
  • Tumor Necrosis Factor-alpha