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

L. C. Hofbauer, D. L. Lacey, C. R. Dunstan, T. C. Spelsberg, B. L. Riggs, S. Khosla

Research output: Contribution to journalArticle

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Abstract

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)-1β, tumor necrosis factor (TNF)-α, 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-1β (5 nmol/L) and TNF-α (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-1β and TNF-α 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-1β and TNF-α, but not IL-6, may stimulate osteoclastogenesis by inducing the expression of OPG-L. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)255-259
Number of pages5
JournalBone
Volume25
Issue number3
DOIs
StatePublished - Sep 1 1999

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Keywords

  • IL-6
  • Interleukin (IL)-1β
  • Osteoblast
  • Osteoprotegerin
  • Osteoprotegerin ligand
  • Tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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