Porphyromonas gingivalis GroEL Induces Osteoclastogenesis of Periodontal Ligament Cells and Enhances Alveolar Bone Resorption in Rats

• Published in: PloS one Vol. 9; no. 7; p. e102450
• Main Authors: Lin, Feng-Yen, Hsiao, Fung-Ping, Huang, Chun-Yao, Shih, Chun-Ming, Tsao, Nai-Wen, Tsai, Chien-Sung, Yang, Shue-Fen, Chang, Nen-Chung, Hung, Shan-Ling, Lin, Yi-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.07.2014; Public Library of Science (PLoS)
• Subjects: Alkaline phosphatase; Alveolar bone; 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; Biocompatibility; Biology; Biology and Life Sciences; Biomedical materials; Bone loss; Bone resorption; Cardiology; Cell activation; Cell migration; Chaperonin 60 - genetics; Chaperonin 60 - metabolism; Chaperonin 60 - pharmacology; Collagen; Computed tomography; Cytokines; Cytoskeleton; Deoxyribonucleic acid; Disease; DNA; Fibroblasts; Gene expression; Gene Expression Regulation; Gum disease; Heart surgery; Heat shock proteins; Homology; Hospitals; Host-Pathogen Interactions; Hsp60 protein; Humans; Integrin alpha1 - genetics; Integrin alpha1 - metabolism; Integrin alpha2 - genetics; Integrin alpha2 - metabolism; Integrins; Interleukin 8; Interleukin-6 - biosynthesis; Interleukin-6 - metabolism; Interleukin-8 - biosynthesis; Interleukin-8 - metabolism; Internal medicine; Ligaments; Male; Medicine; Medicine and Health Sciences; Motility; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Osteoclastogenesis; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Periodontal disease; Periodontal diseases; Periodontal ligament; Periodontal Ligament - microbiology; Periodontal Ligament - pathology; Periodontitis; Periodontitis - genetics; Periodontitis - metabolism; Periodontitis - microbiology; Periodontitis - pathology; Porphyromonas gingivalis; 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; Research and Analysis Methods; Review boards; RNA; Stimulators; TRANCE protein; Virulence; Virulence (Microbiology); Virulence factors; United States > US; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102450

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.