Matrix remodeling response of human periodontal tissue cells toward fibrosis upon nicotine exposure

Hiroko Takeuchi-Igarashi, Satoshi Kubota, Toshiaki Tachibana, Etsuko Murakashi, Masaharu Takigawa, Masataka Okabe, Yukihiro Numabe

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
Issue number1
Publication statusPublished - Jan 1 2016


  • Fibrosis
  • Gingival fibrosis
  • Matrix remodeling
  • Nicotine
  • Smoking

ASJC Scopus subject areas

  • Dentistry(all)


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