title: Matrix remodeling response of human periodontal tissue cells toward fibrosis upon nicotine exposure.
abstract: It is widely accepted that fibrosis is frequently observed in the gingiva of smokers. However, the mechanisms by which smoking results in pathological changes in periodontal tissue that lead to fibrosis are not entirely clear. Our former report showed that type I collagen synthesis was promoted by nicotine via CCN family protein 2 in human periodontal tissue cells. Here, we evaluated other aspects of nicotine function from a viewpoint of extracellular matrix (ECM) remodeling. Human gingival fibroblasts (n = 4) and periodontal ligament cells (n = 3) were isolated. The cells were treated with nicotine at a variety of concentrations for 12-48 h. Modulators of matrix remodeling were measured using enzyme-linked immunosorbent assays. Cell migration and morphology were also evaluated. As a result, following treatment with 1 μg/ml nicotine, tissue inhibitor of metalloproteinase-1 and transforming growth factor-β1 production in both cell lysates and supernatants, and matrix metalloproteinases-1 production in cell lysates, were significantly increased (p < 0.05). Compared to controls, cell migration was significantly inhibited (p < 0.005) by nicotine in a time-dependent manner. Electron microscopic analysis revealed the presence of a number of vacuoles in nicotine-treated cells. These results indicate that nicotine not only impairs fibroblast motility, and induces cellular degenerative changes, but also alters ECM-remodeling systems of periodontal cells. Induction of matrix remodeling molecules, combined with type I collagen accumulation, may account for the molecular mechanism of nicotine-induced periodontal fibrosis.
authors.affiliation: Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan. hiroko.p0324@gmail.com.|Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan. hiroko.p0324@gmail.com.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takeuchi-Igarashi
authors.affiliation: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Division of Fine Morphology, Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Murakashi
authors.affiliation: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takigawa
authors.affiliation: Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okabe
authors.affiliation: Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Numabe
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009538:Nicotine / Q000633:toxicity*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D009538:Nicotine; D020781:Matrix Metalloproteinase 1
keywords: Fibrosis; Gingival fibrosis; Matrix remodeling; Nicotine; Smoking