title: Effect of bacteria on the wound healing behavior of oral epithelial cells.
abstract: Wounded tissue offers opportunity to microflora to adhere, colonize, invade and infect surrounding healthy tissue. The bacteria of the oral cavity have the potential to alter the wound healing process by interacting with keratinocytes. The aim of this study was to investigate mechanisms through which oral bacteria may influence re-epithelialization by interacting with gingival keratinocytes. By an in vitro scratch assay we demonstrate that primary gingival keratinocytes have impaired closure when exposed to two well characterized oral bacteria, P. gingivalis, and to a lesser extent, F. nucleatum. P. gingivalis reduced wound closure by ∼ 40%, which was partially dependent on proteolytic activity, and bacteria was still present within infected cells 9 days later despite exposure to bacteria for only 24 h. Both oral bacteria caused keratinocyte apoptosis at the wound site with cell death being greatest at the wound edge. P. gingivalis and F. nucleatum adversely affected cell proliferation and the effect also had a spatial component being most striking at the edge. The impact of the bacteria was long lasting even when exposure was brief. Cell migration was compromised in bacteria challenged keratinocytes with P. gingivalis having more severe effect (p<0.05) than F. nucleatum. Quantitative real time PCR of bacteria challenged cells showed that P. gingivalis and to a lesser extent F. nucleatum significantly downregulated cell cycle genes cyclin1, CDK1, and CDK4 (p<0.05) that are critical for GI/S transition. Further, genes associated with cell migration such as integrin beta-3 and -6 were significantly downregulated by P. gingivalis (p<0.05).
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Rupa
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ; School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Fanxing
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Implant Dentistry, Peking University, School and Hospital of Stomatology, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Chen
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Ponugoti
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Dana T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology / Q000502:physiology*; D009061:Mouth Mucosa / Q000166:cytology; D016966:Porphyromonas gingivalis / Q000502:physiology; D061251:Primary Cell Culture; D062326:Re-Epithelialization
chemical_list: D016207:Cytokines