Tumor necrosis factor-α mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism

Wei Zou, Imad Hakim, Katharina Tschoep, Stefan Endres, Zvi Bar-Shavit

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Osteoblasts or bone marrow stromal cells are required as supporting cells for the in vitro differentiation of osteoclasts from their progenitor cells. Soluble receptor activator of nuclear factor-κB ligand (RANKL) in the presence of macrophage colony-stimulating factor (M-CSF) is capable of replacing the supporting cells in promoting osteoclastogenesis. In the present study, using Balb/c-derived cultures, osteoclast formation in both systems - osteoblast/bone-marrow cell co-cultures and in RANKL-induced osteoclastogenesis - was inhibited by antibody to tumor necrosis factor-α (TNF-α), and was enhanced by the addition of this cytokine. TNF-α itself promoted osteoclastogenesis in the presence of M-CSF. However, even at high concentrations of TNF-α the efficiency of this activity was much lower than the osteoclastogenic activity of RANKL. RANKL increased the level of TNF-α mRNA and induced TNF-α release from osteoclast progenitors. Furthermore, antibody to p55 TNF-α receptors (TNF receptors-1) (but not to p75 TNF-α receptors (TNF receptors-2) inhibited effectively RANKL- (and TNF-α() induced osteoclastogenesis. Anti-TNF receptors-1 antibody failed to inhibit osteoclastogenesis in C57BL/6-derived cultures. Taken together, our data support the hypothesis that in Balb/c, but not in C57BL/6 (strains known to differ in inflammatory responses and cytokine modulation), TNF-α is an autocrine factor in osteoclasts, promoting their differentiation, and mediates, at least in part, RANKL's induction of osteoclastogenesis.

Original languageEnglish
Pages (from-to)70-83
Number of pages14
JournalJournal of cellular biochemistry
Volume83
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Bone marrow
  • Bone resorption
  • Cytokines
  • Macrophage
  • Osteoblast

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