title: Enterococcus faecalis promotes osteoclastogenesis and semaphorin 4D expression.
abstract: Enterococcus faecalis is considered a major bacterial pathogen implicated in endodontic infections and contributes considerably to periapical periodontitis. This study aimed to investigate the potential mechanisms by which E. faecalis accounts for the bone destruction in periapical periodontitis in vitro. Osteoclast precursor RAW264.7 cells were treated with E. faecalis ATCC 29212 and a wild strain of E. faecalis derived clinically from an infected root canal. The results showed that, to some extent, E. faecalis induced the RAW264.7 cells to form tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast-like cells. This pathogen markedly stimulated RAW264.7 cells to express semaphorin 4D (Sema4D), which inhibits bone formation. Once RAW264.7 cells were primed by low-dose receptor activator of nuclear factor-kappa B ligand (RANKL), E. faecalis could significantly increase the production of TRAP-positive multinucleated cells and up-regulate the expression of osteoclast-specific markers, including NFATc1, TRAP and cathepsin K. Both p38 and ERK1/2 MAPK signaling pathways were activated by E. faecalis in RANKL-primed RAW264.7 cells, and meanwhile the expression of Sema4D was highly increased. In conclusion, E. faecalis may greatly contribute to the bone resorption in periapical periodontitis by promoting RANKL-dependent osteoclastogenesis and expression of Sema4D through activation of p38 and ERK1/2 MAPK signaling pathways.
authors.affiliation: Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China Shenzhen ENT Institute, Shenzhen, Guangdong, China.
authors.forename: Zuhui
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Oral Science, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Chaminda J
authors.initials: CJ
authors.lastname: Seneviratne
authors.affiliation: Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Gary S P
authors.initials: GS
authors.lastname: Cheung
authors.affiliation: Periodontology, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Jin
authors.affiliation: Arthritis and Tissue Degeneration Program, and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, USA Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Baohong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China zhangcf@hku.hk.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001862:Bone Resorption; D002454:Cell Differentiation; D002460:Cell Line; D013293:Enterococcus faecalis / Q000502:physiology*; D005786:Gene Expression Regulation; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000382:microbiology / Q000502:physiology*; D010485:Periapical Periodontitis / Q000209:etiology / Q000503:physiopathology*; D053245:RANK Ligand / Q000276:immunology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D059467:Transcriptome
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; D039961:Semaphorins; D020929:Mitogen-Activated Protein Kinase Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Enterococcus faecalis; MAPK signaling pathways; osteoclasts; receptor activator of nuclear factor-kappa B ligand; tartrate-resistant acid phosphatase