Triclosan blocks MMP-13 expression in hormone-stimulated osteoblasts.
BACKGROUND
Matrix metalloproteinase-13 (MMP-13) is an important enzyme for the modulation of bone turnover and gingival recession. Elevated levels of MMP-13 are associated with alveolar bone resorption, periodontal ligament breakdown, and gingival attachment loss, which are the clinical symptoms of periodontal disease. Evidence continues to suggest that periodontal disease contributes to oral tissue breakdown and is linked to numerous systemic conditions. Triclosan (TCN) is a long-standing, proven antibacterial and anti-inflammatory agent found in the only Food and Drug Administration-approved dentifrice for the treatment of plaque and gingivitis.


METHODS
This study examines the inhibitory effects of TCN on lipopolysaccharide-, parathyroid hormone (PTH)-, and prostaglandin E2 (PGE2)-induced expression of MMP-13 in UMR 106-01 cells, an osteoblastic osteosarcoma cell line. The cells were stimulated with PTH or PGE2 to induce MMP-13 mRNA expression, and real-time reverse transcription-polymerase chain reaction was performed to determine gene expression levels. Western blot analysis assessed the presence or absence of protein degradation or inhibition of protein synthesis. MMP-13 promoter reporter assay was used to explore possible direct effects of TCN on the MMP-13 promoter.


RESULTS
TCN significantly reduced PTH or PGE2 elevated expression of MMP-13 in osteoblastic cells without affecting basal levels of the mRNA. Surprisingly, TCN enhanced the expression of c-fos and amphiregulin mRNA. A promoter assay indicated that TCN directly inhibits the activation of the PTH-responsive minimal promoter of MMP-13.


CONCLUSIONS
The present study appears to have identified a nuclear mechanism of action of TCN that accounts for the ability of TCN to inhibit PTH- or PGE2-induced MMP-13 expression in osteoblastic cells.
Colgate-Palmolive Company Technology Center, Piscataway, NJ.
Virginia Monsul
VM
Barnes
Tao
T
Xu
Emi
E
Shimizu
Teruyo
T
Nakatani
Steven
S
Jefcoat
Anatoliy
A
Vasilov
Ling
L
Qin
Nicola C
NC
Partridge
D066258:Amphiregulin; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000187:drug effects / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology; D066255:EGF Family of Proteins; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006023:Glycoproteins / Q000187:drug effects / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014260:Triclosan / Q000494:pharmacology*
D066258:Amphiregulin; D000891:Anti-Infective Agents, Local; C587850:Areg protein, rat; D050659:Core Binding Factor Alpha 1 Subunit; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D010281:Parathyroid Hormone; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C493717:Runx2 protein, rat; D014260:Triclosan; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D015232:Dinoprostone