Nicotine-induced CCN2: from smoking to periodontal fibrosis.
Since fibrosis is observed in smokers' gingiva, it was hypothesized that fibrosis was caused by nicotine in the periodontium. Therefore, in this study, we investigated the effects of nicotine on the induction of a profibrotic molecule, connective tissue growth factor (CCN2/CTGF), in human gingival fibroblasts (HGFs) and periodontal ligament (PDL) cells. With 1 microg/mL nicotine, vacuolization and attenuated proliferation were observed. Interestingly, 1 microg/mL nicotine increased the production of CCN2/CTGF protein in both cells without increasing mRNA expression. Furthermore, type I collagen mRNA and protein were also increased and were significantly blocked by a CCN2/CTGF neutralizing antibody. This is the first report to describe a relationship between nicotine and CCN2/CTGF in periodontal tissue cells. Analysis of our data also indicated that nicotine was cytotoxic, while it increased CCN2/CTGF and, eventually, type I collagen production. These findings suggest that periodontal fibrosis can be promoted by nicotine from smoking via effects on CCN2/CTGF.
Takeuchi
H
H
Department of Periodontology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. hiroko-p@tky.ndu.ac.jp
Kubota
S
S
Murakashi
E
E
Zhou
Y
Y
Endo
K
K
Ng
P S
PS
Takigawa
M
M
Numabe
Y
Y
D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D055815:Young Adult
D024042:Collagen Type I; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D009538:Nicotine