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, Sundeep Khosla

Research output: Contribution to journalArticle

489 Citations (Scopus)

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 1999

Fingerprint

RANK Ligand
Interleukin-1
Interleukin-6
Tumor Necrosis Factor-alpha
Gene Expression
Stromal Cells
Osteogenesis
Osteoprotegerin
Messenger RNA
Bone Marrow
Cytokines
Cell Line
Interleukin-5
Osteosarcoma
Interleukin-2
Bone and Bones

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. / Hofbauer, L. C.; Lacey, D. L.; Dunstan, C. R.; Spelsberg, T. C.; Riggs, B. L.; Khosla, Sundeep.

In: Bone, Vol. 25, No. 3, 09.1999, p. 255-259.

Research output: Contribution to journalArticle

Hofbauer, L. C. ; Lacey, D. L. ; Dunstan, C. R. ; Spelsberg, T. C. ; Riggs, B. L. ; Khosla, Sundeep. / Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. In: Bone. 1999 ; Vol. 25, No. 3. pp. 255-259.
@article{8f657116e5294036a8de2f84eff1a562,
title = "Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells",
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.",
keywords = "IL-6, Interleukin (IL)-1β, Osteoblast, Osteoprotegerin, Osteoprotegerin ligand, Tumor necrosis factor-α (TNF-α)",
author = "Hofbauer, {L. C.} and Lacey, {D. L.} and Dunstan, {C. R.} and Spelsberg, {T. C.} and Riggs, {B. L.} and Sundeep Khosla",
year = "1999",
month = "9",
doi = "10.1016/S8756-3282(99)00162-3",
language = "English (US)",
volume = "25",
pages = "255--259",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells

AU - Hofbauer, L. C.

AU - Lacey, D. L.

AU - Dunstan, C. R.

AU - Spelsberg, T. C.

AU - Riggs, B. L.

AU - Khosla, Sundeep

PY - 1999/9

Y1 - 1999/9

N2 - 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.

AB - 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.

KW - IL-6

KW - Interleukin (IL)-1β

KW - Osteoblast

KW - Osteoprotegerin

KW - Osteoprotegerin ligand

KW - Tumor necrosis factor-α (TNF-α)

UR - http://www.scopus.com/inward/record.url?scp=0032588998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032588998&partnerID=8YFLogxK

U2 - 10.1016/S8756-3282(99)00162-3

DO - 10.1016/S8756-3282(99)00162-3

M3 - Article

C2 - 10495128

AN - SCOPUS:0032588998

VL - 25

SP - 255

EP - 259

JO - Bone

JF - Bone

SN - 8756-3282

IS - 3

ER -