Inhibition of RANKL-induced osteoclast formation in mouse bone marrow cells by IL-12: Involvement of IFN-γ possibly induced from non-T cell population

Noriko Nagata, Hideki Kitaura, Noriaki Yoshida, Koji Nakayama

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

IL-12 was shown to have the potential to inhibit osteoclast formation in mouse bone marrow cells treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). When bone marrow macrophages (BMM) were used as osteoclast precursors, IL-12 failed to inhibit M-CSF/RANKL-induced osteoclast formation from BMM. In coculture experiments using transwells, IL-12 did inhibit osteoclast formation from BMM cocultured with whole bone marrow cells. These results indicated that IL-12 indirectly affected M-CSF/RANKL-induced osteoclastogenesis in bone marrow cells and that the inhibition of IL-12 on osteoclast formation was caused by a humoral factor from bone marrow cells treated with IL-12. Experiments with anti-interferon (IFN)-γ antibody and bone marrow cells from IFN-γ receptor knockout mice revealed that IFN-γ might be involved in the inhibition of osteoclast formation in this system. The expression of osteoprotegerin mRNA in bone marrow cells was not affected by treatment with IL-12. The inhibitory effect of IL-12 on osteoclast formation was also seen in the T cell-depleted bone marrow cells of normal mice and the whole bone marrow cells of athymic nude mice, while the inhibitory effect of IL-12 was partially suppressed in the B cell-depleted bone marrow cells. The inhibitory effect of IL-12 on M-CSF/RANKL-induced osteoclastogenesis was not accompanied with cell death, in contrast with our previous finding that the inhibitory effect of IL-12 on M-CSF/TNF-α-induced osteoclastogenesis is attributable to Fas and FasL-mediated apoptosis.

Original languageEnglish
Pages (from-to)721-732
Number of pages12
JournalBone
Volume33
Issue number4
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

Keywords

  • Bone marrow
  • Cytokines
  • Osteoclasts

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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