The hemoglobin receptor protein of Porphyromonas gingivalis inhibits receptor activator NF-κB ligand-induced osteoclastogenesis from bone marrow macrophages

Yuji Fujimura, Hitoshi Hotokezaka, Naoya Ohara, Mariko Naito, Eiko Sakai, Mamiko Yoshimura, Yuka Narita, Hideki Kitaura, Noriaki Yoshida, Koji Nakayama

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Extracellular proteinaceous factors of Porphyromonas gingivalis, a periodontal pathogen, that influence receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis from bone marrow macrophages were investigated. The culture supernatant of P. gingivalis had the ability to inhibit RANKL-induced in vitro osteoclastogenesis. A major protein of the culture supernatant, hemoglobin receptor protein (HbR), suppressed RANKL-induced osteoclastogenesis in a dose-dependent fashion. HbR markedly inhibited RANKL-induced osteoclastogenesis when present in the culture for the first 24 h after addition of RANKL, whereas no significant inhibition was observed when HbR was added after 24 h or later, implying that HbR might interfere with only the initial stage of RANKL-mediated differentiation. HbR tightly bound to bone marrow macrophages and had the ability to induce phosphorylation of ERK, p38, NF-κB, and Akt. RANKL-induced phosphorylation of ERK, p38, and NF-κB was not suppressed by HbR, but that of Akt was markedly suppressed. HbR inhibited RANKL-mediated induction of c-Fos and NFATc1. HbR could induce beta interferon (IFN-β) from bone marrow macrophages, but the induction level of IFN-β might not be sufficient to suppress RANKL-mediated osteoclastogenesis, implying presence of an IFN-β- independent pathway in HbR-mediated inhibition of osteoclastogenesis. Since rapid and extensive destruction of the alveolar bone causes tooth loss, resulting in loss of the gingival crevice that is an anatomical niche for periodontal pathogens such as P. gingivalis, the suppressive effect of HbR on osteoclastogenesis may help the microorganism exist long in the niche.

Original languageEnglish
Pages (from-to)2544-2551
Number of pages8
JournalInfection and Immunity
Volume74
Issue number5
DOIs
Publication statusPublished - May 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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