Extracellular β-NAD+ inhibits interleukin-1-induced matrix metalloproteinase-1 and -3 expression on human gingival fibroblasts

Kazuhiro Gotoh, Eiji Nemoto, Sousuke Kanaya, Hidetoshi Shimauchi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


There is increasing evidence to show that extracellular β-nicotinamide adenine dinucleotide (β-NAD+) modulates various biological functions in inflammatory/immune regions. The aim of this study was to determine the effect of β-NAD+ on matrix metalloproteinase (MMP) expression on human gingival fibroblasts (hGF), the excess production of which leads to the matrix degradation associated with the pathological processes of periodontitis. The expression of MMP-1 and MMP-3 on hGF was determined by real-time polymerase chain reaction (PCR) and an enzyme-linked immunosorbent assay. The phosphorylated status of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38 and the expression of inhibitor κB (IκB)α were determined by Western blotting. β-NAD+ inhibited the expression of MMP-1 and MMP-3 triggered by IL-1α at gene and protein levels. β-NAD+ had no significant effect on the IL-1α-induced phosphorylation of ERK1/2, JNK, and p38 and also had no effect on the IL-1α-induced degradation of IκBα relative to the control, suggesting that inhibition by β-NAD+ was independent of the MAP kinase and the nuclear factor-κB signaling pathways. Transcripts of NAD+-metabolizing enzymes, such as NAD+-glycohydrolase, adenosine diphosphate (ADP)-ribosylcyclase, and ADP-ribosyltransferase, were expressed by hGF as assessed by RT-PCR. Experiments using α-NAD +, which is not a substrate for ADP-ribosylcyclase or ADP-ribosyltransferase, revealed the possible contribution of NAD +-glycohydrolase to the inhibition of MMP. This is consistent with the finding that ADP-ribose, an NAD+-metabolite by NAD +-glycohydrolase, exhibited MMP inhibition similar to β-NAD +. The present findings may provide an additional viewpoint to clarify a natural feedback mechanism during the inflammatory process in periodontal tissue.

Original languageEnglish
Pages (from-to)204-209
Number of pages6
JournalConnective Tissue Research
Issue number3
Publication statusPublished - 2013


  • Ectoenzyme
  • Gingival fibroblast
  • Inflammation
  • Matrix metalloproteinase
  • NAD
  • Periodontal tissue

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology


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