Abstract
The mechanism of osteoclast-like cell formation induced by periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (serotype b) capsular-polysaccharide-like polysaccharide (capsular-like polysaccharide) was examined in a mouse bone marrow culture system. When mouse bone marrow cells were cultured with A. actinomycetemcomitans Y4 capsular-like polysaccharide for 9 days, many multinucleated cells were formed. The multinucleated cells showed several characteristics of osteoclasts, including tartrate-resistant acid phosphatase (TRACP) and the ability to resorb the calcified dentine. In this study, we examined the effects of antisera to interleukins on the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Monospecific anti-mouse recombinant interleukin-1 alpha (rIL-1 alpha) serum completely inhibited the formation of osteoclast-like cells in the presence of A. actinomycetemcomitans Y4 capsular-like polysaccharide. However, anti-mouse rIL-1 beta and anti-mouse rIL-6 sera showed no effect on osteoclast-like cell formation. IL-1 receptor antagonist significantly inhibited the osteoclast-like cell formation mediated by A. actinomycetemcomitans Y4 capsular-like polysaccharide in mouse marrow cultures. The bioactive IL-1 was detected in the culture media of mouse bone marrow cells stimulated with A. actinomycetemcomitans Y4 capsular-like polysaccharide. These results indicate that IL-1 alpha is involved in the mechanism of the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. We sought to determine whether osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide could be modulated by the protein kinase inhibitors H8 and HA1004. The formation of osteoclast-like cells was suppressed by H8 and HA1004. These findings suggest that the signals by protein kinases may regulate osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Furthermore, a correlation between IL-1 alpha and prostaglandin E2 in the osteoclast recruitment induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide is discussed.
Full Text
The Full Text of this article is available as a PDF (563.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akatsu T., Takahashi N., Debari K., Morita I., Murota S., Nagata N., Takatani O., Suda T. Prostaglandins promote osteoclastlike cell formation by a mechanism involving cyclic adenosine 3',5'-monophosphate in mouse bone marrow cell cultures. J Bone Miner Res. 1989 Feb;4(1):29–35. doi: 10.1002/jbmr.5650040106. [DOI] [PubMed] [Google Scholar]
- Akatsu T., Takahashi N., Udagawa N., Imamura K., Yamaguchi A., Sato K., Nagata N., Suda T. Role of prostaglandins in interleukin-1-induced bone resorption in mice in vitro. J Bone Miner Res. 1991 Feb;6(2):183–189. doi: 10.1002/jbmr.5650060212. [DOI] [PubMed] [Google Scholar]
- Amano K., Nishihara T., Shibuya N., Noguchi T., Koga T. Immunochemical and structural characterization of a serotype-specific polysaccharide antigen from Actinobacillus actinomycetemcomitans Y4 (serotype b). Infect Immun. 1989 Oct;57(10):2942–2946. doi: 10.1128/iai.57.10.2942-2946.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garrison S. W., Holt S. C., Nichols F. C. Lipopolysaccharide-stimulated PGE2 release from human monocytes. Comparison of lipopolysaccharides prepared from suspected periodontal pathogens. J Periodontol. 1988 Oct;59(10):684–687. doi: 10.1902/jop.1988.59.10.684. [DOI] [PubMed] [Google Scholar]
- Gmür R., McNabb H., van Steenbergen T. J., Baehni P., Mombelli A., van Winkelhoff A. J., Guggenheim B. Seroclassification of hitherto nontypeable Actinobacillus actinomycetemcomitans strains: evidence for a new serotype e. Oral Microbiol Immunol. 1993 Apr;8(2):116–120. doi: 10.1111/j.1399-302x.1993.tb00556.x. [DOI] [PubMed] [Google Scholar]
- Gowen M., Mundy G. R. Actions of recombinant interleukin 1, interleukin 2, and interferon-gamma on bone resorption in vitro. J Immunol. 1986 Apr 1;136(7):2478–2482. [PubMed] [Google Scholar]
- Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
- Iino Y., Hopps R. M. The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths. Arch Oral Biol. 1984;29(1):59–63. doi: 10.1016/0003-9969(84)90043-8. [DOI] [PubMed] [Google Scholar]
- Ishimi Y., Miyaura C., Jin C. H., Akatsu T., Abe E., Nakamura Y., Yamaguchi A., Yoshiki S., Matsuda T., Hirano T. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol. 1990 Nov 15;145(10):3297–3303. [PubMed] [Google Scholar]
- Kiley P., Holt S. C. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun. 1980 Dec;30(3):862–873. doi: 10.1128/iai.30.3.862-873.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loh C. L., Rotondo D., Dutta-Roy A. K. Characterization of prostaglandin E2 receptors expressed on human monocytic leukaemic cell line, U937. Biochim Biophys Acta. 1993 May 8;1177(1):43–48. doi: 10.1016/0167-4889(93)90155-i. [DOI] [PubMed] [Google Scholar]
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
- Nishihara T., Ohsaki Y., Ueda N., Saito N., Mundy G. R. Mouse interleukin-1 receptor antagonist induced by Actinobacillus actinomycetemcomitans lipopolysaccharide blocks the effects of interleukin-1 on bone resorption and osteoclast-like cell formation. Infect Immun. 1994 Feb;62(2):390–397. doi: 10.1128/iai.62.2.390-397.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson P. B., Lantz M., Marucha P. T., Kornman K. S., Trummel C. L., Holt S. C. Collagenolytic activity associated with Bacteroides species and Actinobacillus actinomycetemcomitans. J Periodontal Res. 1982 May;17(3):275–283. doi: 10.1111/j.1600-0765.1982.tb01154.x. [DOI] [PubMed] [Google Scholar]
- Saarela M., Asikainen S., Alaluusua S., Pyhälä L., Lai C. H., Jousimies-Somer H. Frequency and stability of mono- or poly-infection by Actinobacillus actinomycetemcomitans serotypes a, b, c, d or e. Oral Microbiol Immunol. 1992 Oct;7(5):277–279. doi: 10.1111/j.1399-302x.1992.tb00588.x. [DOI] [PubMed] [Google Scholar]
- Sims T. J., Moncla B. J., Darveau R. P., Page R. C. Antigens of Actinobacillus actinomycetemcomitans recognized by patients with juvenile periodontitis and periodontally normal subjects. Infect Immun. 1991 Mar;59(3):913–924. doi: 10.1128/iai.59.3.913-924.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slots J., Genco R. J. Black-pigmented Bacteroides species, Capnocytophaga species, and Actinobacillus actinomycetemcomitans in human periodontal disease: virulence factors in colonization, survival, and tissue destruction. J Dent Res. 1984 Mar;63(3):412–421. doi: 10.1177/00220345840630031101. [DOI] [PubMed] [Google Scholar]
- Suda T., Takahashi N., Martin T. J. Modulation of osteoclast differentiation. Endocr Rev. 1992 Feb;13(1):66–80. doi: 10.1210/edrv-13-1-66. [DOI] [PubMed] [Google Scholar]
- Taichman N. S., Dean R. T., Sanderson C. J. Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans. Infect Immun. 1980 Apr;28(1):258–268. doi: 10.1128/iai.28.1.258-268.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi N., Yamana H., Yoshiki S., Roodman G. D., Mundy G. R., Jones S. J., Boyde A., Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988 Apr;122(4):1373–1382. doi: 10.1210/endo-122-4-1373. [DOI] [PubMed] [Google Scholar]
- Takahashi T., Nishihara T., Ishihara Y., Amano K., Shibuya N., Moro I., Koga T. Murine macrophage interleukin-1 release by capsularlike serotype-specific polysaccharide antigens of Actinobacillus actinomycetemcomitans. Infect Immun. 1991 Jan;59(1):18–23. doi: 10.1128/iai.59.1.18-23.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tamura T., Udagawa N., Takahashi N., Miyaura C., Tanaka S., Yamada Y., Koishihara Y., Ohsugi Y., Kumaki K., Taga T. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11924–11928. doi: 10.1073/pnas.90.24.11924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsai C. C., Shenker B. J., DiRienzo J. M., Malamud D., Taichman N. S. Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B. Infect Immun. 1984 Feb;43(2):700–705. doi: 10.1128/iai.43.2.700-705.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Udagawa N., Takahashi N., Akatsu T., Tanaka H., Sasaki T., Nishihara T., Koga T., Martin T. J., Suda T. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7260–7264. doi: 10.1073/pnas.87.18.7260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vandenabeele P., Declercq W., Libert C., Fiers W. Development of a simple, sensitive and specific bioassay for interleukin-1 based on the proliferation of RPMI 1788 cells. Comparison with other bioassays for IL-1. J Immunol Methods. 1990 Dec 31;135(1-2):25–32. doi: 10.1016/0022-1759(90)90252-q. [DOI] [PubMed] [Google Scholar]
- Wilson M., Kamin S., Harvey W. Bone resorbing activity of purified capsular material from Actinobacillus actinomycetemcomitans. J Periodontal Res. 1985 Sep;20(5):484–491. doi: 10.1111/j.1600-0765.1985.tb00831.x. [DOI] [PubMed] [Google Scholar]
- Zambon J. J. Actinobacillus actinomycetemcomitans in human periodontal disease. J Clin Periodontol. 1985 Jan;12(1):1–20. doi: 10.1111/j.1600-051x.1985.tb01348.x. [DOI] [PubMed] [Google Scholar]
- Zambon J. J., Christersson L. A., Genco R. J. Diagnosis and treatment of localized juvenile periodontitis. J Am Dent Assoc. 1986 Aug;113(2):295–299. doi: 10.14219/jada.archive.1986.0152. [DOI] [PubMed] [Google Scholar]
- Zambon J. J., Christersson L. A., Slots J. Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotypes within families. J Periodontol. 1983 Dec;54(12):707–711. doi: 10.1902/jop.1983.54.12.707. [DOI] [PubMed] [Google Scholar]
- Zambon J. J., Slots J., Genco R. J. Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease. Infect Immun. 1983 Jul;41(1):19–27. doi: 10.1128/iai.41.1.19-27.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]