DOI QR코드

DOI QR Code

Augmented Osteoclastogenesis from Committed Osteoclast Precursors by Periodontopathic Bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis

치주염 유발 세균 Aggregatibacter actinomycetemcomitans와 Porphyromonas gingivalis에 의한 committed osteoclast precursor 분화 증가

  • Park, Ok-Jin (Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry) ;
  • Kwon, Yeongkag (Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry) ;
  • Yun, Cheol-Heui (Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University) ;
  • Han, Seung Hyun (Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry)
  • 박옥진 (서울대학교 치의학대학원 구강미생물.면역학교실) ;
  • 권영각 (서울대학교 치의학대학원 구강미생물.면역학교실) ;
  • 윤철희 (서울대학교 농업생명과학대학 농생명공학부 동물생명공학전공) ;
  • 한승현 (서울대학교 치의학대학원 구강미생물.면역학교실)
  • Received : 2016.08.31
  • Accepted : 2016.09.21
  • Published : 2016.12.28

Abstract

Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis are gram-negative bacteria frequently found in lesions from patients with periodontitis manifesting alveolar bone loss. Lipopolysaccharides are a major virulence factor of gram-negative bacteria. Bone resorption is known to be regulated by bacteria and their virulence factors. In the present study, we investigated the effects of A. actinomycetemcomitans and P. gingivalis on bone resorption. Heat-killed A. actinomycetemcomitans (HKAa) and heatkilled P. gingivalis (HKPg) induced bone loss in the femurs of mice after intraperitoneal administration. HKAa and HKPg augmented the differentiation of committed osteoclast precursors into osteoclasts, while they inhibited the differentiation of bone marrow-derived macrophages into osteoclasts. Concordant with the effects of the heat-killed whole cells, LPS purified from A. actinomycetemcomitans and P. gingivalis also augmented osteoclast differentiation from committed osteoclast precursors but attenuated it from bone marrow-derived macrophages. Taken together, these results suggest that the whole cells and lipopolysaccharides of A. actinomycetemcomitans and P. gingivalis induce the differentiation of committed osteoclast precursors into osteoclasts, potentially contributing to bone resorption in vivo.

치주질환은 만성염증성 질환으로 치조골소실을 일으켜 성인치아상실을 유발하는 요인 중 하나이다. 그람 음성세균인 Aggregatibacter actinomycetemcomitans와 Porphyromonas gingivalis는 치주질환환자의 병소에서 쉽게 동정된다. 지질다당체(Lipopolysaccharide; LPS)는 그람 음성세균의 핵심 독력인자로 알려져 있다. 이러한 세균과 LPS는 파골세포에 의한 골소실을 조절하는 요인 중 하나이다. 그러므로 본 연구에서는 동물모델을 활용하여 A. actinomycetemcomitans와 P. gingivalis의 의한 골소실 여부를 확인하고, 기전규명을 위하여 A. actinomycetemcomitans, P. gingivalis, A. actinomycetemcomitans와 P. gingivalis에서 분리한 LPS에 의한 파골세포분화 영향을 연구하였다. 열사멸한 A. actinomycetemcomitans (HKAa)와 열사멸한 P. gingivalis (HKPg)가 복강으로 투여된 쥐의 대퇴골은 대조군에 비해 감소된 골량을 보여주었다. 이러한 골소실의 증가가 파골세포분화 때문인지 확인하기 위해 파골세포분화를 연구한 결과, bone marrow-derived macrophage (BMM)의 RANKL-매개 파골세포분화를 감소시켰으나, committed osteoclast precursor의 파골세포분화를 유도함을 확인하였다. 세균에 의한 파골세포분화 결과와 동일하게 A. actinomycetemcomitans와 P. gingivalis에서 분리한 LPS 역시 RANKL-매개 파골세포분화는 감소시키고, committed osteoclast precursor의 파골세포분화를 유도하였다. 결과적으로 치주원인균인 A. actinomycetemcomitans와 P. gingivalis는 committed osteoclast precursor의 파골세포분화를 증가시키는데, 이 세균들의 LPS가 핵심 역할을 수행하는 것으로 판단되며 이를 통해 골 흡수를 유발함을 알 수 있었다.

Keywords

References

  1. Arai F, Miyamoto T, Ohneda O, Inada T, Sudo T, Brasel K, et al. 1999. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J. Exp. Med. 190: 1741-1754. https://doi.org/10.1084/jem.190.12.1741
  2. Feng X, McDonald JM. 2011. Disorders of bone remodeling. Annu. Rev. Pathol. 6: 121-145. https://doi.org/10.1146/annurev-pathol-011110-130203
  3. Flemmig TF. 1999. Periodontitis. Ann. Periodontol. 4: 32-38. https://doi.org/10.1902/annals.1999.4.1.32
  4. Irfan UM, Dawson DV, Bissada NF. 2001. Epidemiology of periodontal disease: a review and clinical perspectives. J. Int. Acad Periodontol. 3: 14-21.
  5. Kang J, de Brito Bezerra B, Pacios S, Andriankaja O, Li Y, Tsiagbe V, et al. 2012. Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis. Infect. Immun. 80: 2247-2256. https://doi.org/10.1128/IAI.06371-11
  6. Kim J, Yang J, Park OJ, Kang SS, Kim WS, Kurokawa K, et al. 2013. Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation. J. Bone. Miner. Res. 28: 2381-2391. https://doi.org/10.1002/jbmr.1973
  7. Kopydlowski KM, Salkowski CA, Cody MJ, van Rooijen N, Major J, Hamilton TA, Vogel SN. 1999. Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. J. Immunol. 163: 1537-1544.
  8. McArdle A, Marecic O, Tevlin R, Walmsley GG, Chan CK, Longaker MT, et al. 2015. The role and regulation of osteoclasts in normal bone homeostasis and in response to injury. Plast. Reconstr. Surg. 135: 808-816. https://doi.org/10.1097/PRS.0000000000000963
  9. Mogensen TH. 2009. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 22: 240-273. https://doi.org/10.1128/CMR.00046-08
  10. Munford RS. 2008. Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect. Immun. 76: 454-465. https://doi.org/10.1128/IAI.00939-07
  11. Papapanou PN. 1996. Periodontal diseases: epidemiology. Ann. Periodontol. 1: 1-36. https://doi.org/10.1902/annals.1996.1.1.1
  12. Park OJ, Cho MK, Yun CH, Han SH. 2015. Lipopolysaccharide of Aggregatibacter actinomycetemcomitans induces the expression of chemokines MCP-1, MIP-1alpha, and IP-10 via similar but distinct signaling pathways in murine macrophages. Immunobiology 220: 1067-1074. https://doi.org/10.1016/j.imbio.2015.05.008
  13. Park OJ, Yang J, Kim J, Yun CH, Han SH. 2015. Enterococcus faecalis attenuates the differentiation of macrophages into osteoclasts. J. Endod. 41: 658-662. https://doi.org/10.1016/j.joen.2014.12.015
  14. Park OJ, Yi H, Jeon JH, Kang SS, Koo KT, Kum KY, et al. 2015. Pyrosequencing analysis of subgingival microbiota in distinct periodontal conditions. J. Dent. Res. 94: 921-927. https://doi.org/10.1177/0022034515583531
  15. Ready D, D'Aiuto F, Spratt DA, Suvan J, Tonetti MS, Wilson M. 2008. Disease severity associated with presence in subgingival plaque of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia, singly or in combination, as detected by nested multiplex PCR. J. Clin. Microbiol. 46: 3380-3383. https://doi.org/10.1128/JCM.01007-08
  16. Rodan GA. 1998. Bone homeostasis. Proc. Natl. Acad. Sci. USA 95: 13361-13362. https://doi.org/10.1073/pnas.95.23.13361
  17. Rogers JE, Li F, Coatney DD, Rossa C, Bronson P, Krieder JM, et al. 2007. Actinobacillus actinomycetemcomitans lipopolysaccharide-mediated experimental bone loss model for aggressive periodontitis. J. Periodontol. 78: 550-558. https://doi.org/10.1902/jop.2007.060321
  18. Takami M, Kim N, Rho J, Choi Y. 2002. Stimulation by toll-like receptors inhibits osteoclast differentiation. J. Immunol. 169: 1516-1523. https://doi.org/10.4049/jimmunol.169.3.1516
  19. Trouillet-Assant S, Gallet M, Nauroy P, Rasigade JP, Flammier S, Parroche P, et al. 2015. Dual impact of live Staphylococcus aureus on the osteoclast lineage, leading to increased bone resorption. J. Infect. Dis. 211: 571-581. https://doi.org/10.1093/infdis/jiu386
  20. Van Dyke TE, Sheilesh D. 2005. Risk factors for periodontitis. J. Int. Acad. Periodontol. 7: 3-7.
  21. Varoga D, Wruck CJ, Tohidnezhad M, Brandenburg L, Paulsen F, Mentlein R, et al. 2009. Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3. Histochem. Cell Biol. 131: 207-218. https://doi.org/10.1007/s00418-008-0522-8
  22. Wright JA, Nair SP. 2010. Interaction of staphylococci with bone. Int. J. Med. Microbiol. 300: 193-204. https://doi.org/10.1016/j.ijmm.2009.10.003
  23. Zhang W, Ju J, Rigney T, Tribble G. 2014. Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model. BMC Oral. Health. 14: 89. https://doi.org/10.1186/1472-6831-14-89
  24. Zou W, Bar-Shavit Z. 2002. Dual modulation of osteoclast differentiation by lipopolysaccharide. J. Bone. Miner. Res. 17: 1211-1218. https://doi.org/10.1359/jbmr.2002.17.7.1211