CpG oligonucleotides: Novel regulators of osteoclast differentiation

W. E.I. Zou, Harry Schwartz, Stefan Endres, Gunther Hartmann, Z. V.I. Bar-Shavit

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46 Scopus citations

Abstract

The macrophage capability to recognize bacterial DNA is mimicked by oligodeoxynucleotides containing unmethylated CG dinucleotides ('CpG' motifs) in specific sequence contexts (CpG ODN). CpG ODN stimulates NF-κB activation in murine macrophages. In light of the pivotal role played by NF-κB in osteoclast differentiation, we examined the ability of CpG ODN to modulate osteoclastogenesis. CpG ODN alone induced TRAP-positive cells in bone marrow macrophage (BMM) cultures, but not multinucleation or calcitonin receptor expression. CpG ODN inhibited RANKL-induced osteoclastogenesis when present from the beginning of BMM culture, but strongly increased RANKL-induced osteoclastogenesis in RANKL-pre-treated BMMs. CpG ODN enhanced the expression of interleukin 1β (IL-1β) and tumor necrosis factor (TNF-α). Antibodies to TNF-α and the TNF type 1 receptor, but not the addition of IL-1 receptor antagonist, blocked CpG ODN-induced osteoclastogenesis in RANKL-pretreated cultures. On the other hand, CpG ODN reduced expression of the M-CSF receptor, which is critical during the initiation of osteoclast differentiation. These results suggest that CpG ODN, via the induction of TNF-α, support osteoclastogenesis in cells that are committed to the osteoclast differentiation pathway but, due to down-modulation of M-CSF receptor, inhibit early steps of osteoclast differentiation. Thus, CpG ODN represents a potential therapeutic tool for treating bone diseases.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalFASEB Journal
Volume16
Issue number3
DOIs
StatePublished - Mar 14 2002
Externally publishedYes

Keywords

  • Bone
  • Immunostimulatory oligodexynucleotide
  • M-CSF
  • RANKL
  • TNF-α

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    Zou, W. E. I., Schwartz, H., Endres, S., Hartmann, G., & Bar-Shavit, Z. V. I. (2002). CpG oligonucleotides: Novel regulators of osteoclast differentiation. FASEB Journal, 16(3), 274-282. https://doi.org/10.1096/fj.01-0586com