This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fujimura, Y. Articles by Nakayama, K. Search for Related Content PubMed PubMed Citation Articles by Fujimura, Y. Articles by Nakayama, K.

 Previous Article  |  Next Article 

Infection and Immunity, May 2006, p. 2544-2551, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2544-2551.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Hemoglobin Receptor Protein of Porphyromonas gingivalis Inhibits Receptor Activator NF-B Ligand-Induced Osteoclastogenesis from Bone Marrow Macrophages

Yuji Fujimura,^1,2 Hitoshi Hotokezaka,² Naoya Ohara,¹ Mariko Naito,¹ Eiko Sakai,³ Mamiko Yoshimura,¹ Yuka Narita,³ Hideki Kitaura,² Noriaki Yoshida,² and Koji Nakayama^1*

Divisions of Microbiology and Oral Infection,¹ Orthodontic and Biomedical Engineering,² Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan³

Received 5 July 2005/ Returned for modification 21 December 2005/ Accepted 6 February 2006

Extracellular proteinaceous factors of Porphyromonas gingivalis, a periodontal pathogen, that influence receptor activator of nuclear factor-B (NF-B) 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-B, and Akt. RANKL-induced phosphorylation of ERK, p38, and NF-B 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-ß) from bone marrow macrophages, but the induction level of IFN-ß might not be sufficient to suppress RANKL-mediated osteoclastogenesis, implying presence of an IFN-ß-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.

---

* Corresponding author. Mailing address: Division of Microbiology and Oral Infection, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. Phone: 81-95-849-7648. Fax: 81-95-849-7650. E-mail: knak{at}net.nagasaki-u.ac.jp.

Editor: V. J. DiRita

---

Infection and Immunity, May 2006, p. 2544-2551, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2544-2551.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Sato, K., Kido, N., Murakami, Y., Hoover, C. I., Nakayama, K., Yoshimura, F. (2009). Lipopolysaccharide biosynthesis-related genes are required for colony pigmentation of Porphyromonas gingivalis. Microbiology 155: 1282-1293 [Abstract] [Full Text]