Enterococcus faecalis promotes osteoclastogenesis and semaphorin 4D expression
Authors: Lijian Jin
Chengfei Zhang
Shuai Wang
Chaminda J Seneviratne
Gary S P Cheung
Baohong Zhao
Zuhui Deng
Journal: Innate immunity (2015)
Discipline: IMMUNOLOGY
Keywords: Enterococcus faecalis; MAPK signaling pathways; osteoclasts; receptor activator of nuclear factor-kappa B ligand; tartrate-resistant acid phosphatase.
Affiliations: Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China., Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China Shenzhen ENT Institute, Shenzhen, Guangdong, China., Oral Science, Faculty of Dentistry, National University of Singapore, Singapore., Periodontology, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China., 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., Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China .

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. 

Retracted: No

PubPeer comments:
 Figure 3B. * Green boxes: The ATCC29212 MOI1000 panel appears to show an overlap with the P25RC MOI100 panel. ![file] , 
 #1 Thank you very much for your comment. We have carefully re-checked all the raw data of TRAP staining pictures of Figure 3 (b), which include 72 images in total (We took nine random fields of each group and use one image from each group for this paper). We found that the original image of P25RC MOI 100 was indeed mistakenly inserted and that was the same as the picture of ATCC 29212 MOI 1000. When we prepared the images for publication, we made the images arrangement using PPT. All the pictures were inserted in PPT. We used the top left corner part of the pictures in this paper. The figure of P25RC MOI 100 was misplaced during the computer operations. Unfortunately, we didnu2019t realize this mistake in time. The original images of ATCC 29212 MOI 1000 and P25RC MOI 100 were attached here, as well as the screen shots of all the TRAP staining pictures. We apologize for this carelessness. We have only replaced the image of P25RC MOI 100 with the right one as attached Figure 3. We highly appreciated your work for scientific research environment. We will contact Innate Immunity soon and correct this figure. Chengfei ZHANG![file] ![file] ![file] ![file] ![file] ![file] ![file] , 
 Dear Dr. Zhang, thank you so much for your prompt answer, and for finding the old original photos. Thank you for correcting the literature! , 
 Correction, July 2020: https: journals.sagepub.com doi 10.1177 1753425920926284  In the above referenced article, the authors have identified that the image of P25RC MOI 100 in Figure 3(b) was incorrect. The authors apologize for this error. The correct image of P25RC MOI 100 is shown here. I thank the authors and the journal for correcting this issue. ,