Porphyromonas gingivalis GroEL induces osteoclastogenesis of periodontal ligament cells and enhances alveolar bone resorption in rats

Feng-Yen Lin; Fung-Ping Hsiao; Chun-Yao Huang; Chun-Ming Shih; Nai-Wen Tsao; Chien-Sung Tsai; Shue-Fen Yang; Nen-Chung Chang; Shan-Ling Hung; Yi-Wen Lin

doi:10.1371/journal.pone.0102450

Porphyromonas gingivalis GroEL induces osteoclastogenesis of periodontal ligament cells and enhances alveolar bone resorption in rats

PLoS One. 2014 Jul 24;9(7):e102450. doi: 10.1371/journal.pone.0102450. eCollection 2014.

Authors

Affiliations

¹ Division of Cardiology, Taipei Medical University Hospital, Taipei, Taiwan; Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
³ Division of Cardiovascular Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
⁴ Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁵ Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶ Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.

Abstract

Porphyromonas gingivalis is a major periodontal pathogen that contains a variety of virulence factors. The antibody titer to P. gingivalis GroEL, a homologue of HSP60, is significantly higher in periodontitis patients than in healthy control subjects, suggesting that P. gingivalis GroEL is a potential stimulator of periodontal disease. However, the specific role of GroEL in periodontal disease remains unclear. Here, we investigated the effect of P. gingivalis GroEL on human periodontal ligament (PDL) cells in vitro, as well as its effect on alveolar bone resorption in rats in vivo. First, we found that stimulation of PDL cells with recombinant GroEL increased the secretion of the bone resorption-associated cytokines interleukin (IL)-6 and IL-8, potentially via NF-κB activation. Furthermore, GroEL could effectively stimulate PDL cell migration, possibly through activation of integrin α1 and α2 mRNA expression as well as cytoskeletal reorganization. Additionally, GroEL may be involved in osteoclastogenesis via receptor activator of nuclear factor κ-B ligand (RANKL) activation and alkaline phosphatase (ALP) mRNA inhibition in PDL cells. Finally, we inoculated GroEL into rat gingiva, and the results of microcomputed tomography (micro-CT) and histomorphometric assays indicated that the administration of GroEL significantly increased inflammation and bone loss. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to osteoclastogenesis of PDL cells and resulting in periodontal disease with alveolar bone resorption.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alveolar Bone Loss / genetics
Alveolar Bone Loss / metabolism
Alveolar Bone Loss / microbiology*
Alveolar Bone Loss / pathology
Animals
Bacterial Proteins / genetics*
Bacterial Proteins / metabolism
Bacterial Proteins / pharmacology
Chaperonin 60 / genetics*
Chaperonin 60 / metabolism
Chaperonin 60 / pharmacology
Gene Expression Regulation
Host-Pathogen Interactions
Humans
Integrin alpha1 / genetics
Integrin alpha1 / metabolism
Integrin alpha2 / genetics
Integrin alpha2 / metabolism
Interleukin-6 / biosynthesis
Interleukin-6 / metabolism
Interleukin-8 / biosynthesis
Interleukin-8 / metabolism
Male
NF-kappa B / genetics
NF-kappa B / metabolism
Osteoclasts / drug effects
Osteoclasts / metabolism
Osteoclasts / pathology*
Periodontal Ligament / microbiology*
Periodontal Ligament / pathology
Periodontitis / genetics
Periodontitis / metabolism
Periodontitis / microbiology*
Periodontitis / pathology
Porphyromonas gingivalis / genetics
Porphyromonas gingivalis / metabolism
Porphyromonas gingivalis / pathogenicity
RANK Ligand / genetics
RANK Ligand / metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology

Substances

Bacterial Proteins
Chaperonin 60
IL6 protein, human
Integrin alpha1
Integrin alpha2
Interleukin-6
Interleukin-8
NF-kappa B
RANK Ligand
Recombinant Proteins
TNFSF11 protein, human

Grants and funding

This work was supported by National Science Council (NSC 101-2314 B-038-041-MY3), Taiwan. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.