Interleukin-1beta and tumor necrosis factor-alpha, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells

Bone. 1999 Sep;25(3):255-9. doi: 10.1016/s8756-3282(99)00162-3.


Recent studies have identified osteoprotegerin ligand (OPG-L) as the essential factor required for osteoclastogenesis, and that the effects are prevented by its soluble receptor, osteoprotegerin (OPG). However, there are limited data at present on the regulation of OPG-L expression in human osteoblastic cells by other cytokines. Because interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 all increase osteoclastogenesis, we assessed whether OPG-L mRNA steady-state levels were regulated by these cytokines in human osteoblastic cells. By northern analysis, IL-1beta (5 nmol/L) and TNF-alpha (9 nmol/L) increased OPG-L mRNA steady-state levels by up to two- to three-fold in normal marrow stromal cells (MS), an immortalized marrow stromal cell line (hMS), and the osteosarcoma cell line, MG-63, whereas IL-6 (2 nmol/L, with or without its soluble receptor) had no effect on OPG-L mRNA levels in any of these cells. IL-1beta and TNF-alpha increased OPG-L mRNA steady-state levels in the normal MS cells and the hMS cell line in a time- and dose-dependent fashion by up to 4.1-fold and up to 2.6-fold, respectively. Our data are thus consistent with the hypothesis that the proinflammatory and bone-resorbing cytokines, IL-1beta and TNF-alpha, but not IL-6, may stimulate osteoclastogenesis by inducing the expression of OPG-L.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Cell Line, Transformed
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / pharmacology*
  • Ligands
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • RANK Ligand
  • RNA, Messenger / metabolism
  • Receptor Activator of Nuclear Factor-kappa B
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Carrier Proteins
  • Interleukin-1
  • Interleukin-6
  • Ligands
  • Membrane Glycoproteins
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha